If you don't get blisters ever, feel free to skip this. I used to get blisters especially from racing and I hated it. I can stay cheerful through all kinds physical difficulties from either end of the GI tract to cramping to late night delusions. Blisters just *#@#**# tick me off. I read all sorts of blogs and product reviews during my first year running ultras and I performed all sorts of experiments on myself. Here's a summary of the things that make a difference for me.
1) The fit of my shoes. I used to wear my shoes tighter, thinking that I would have more stability and that less movement would mean fewer blisters. Your shoe will always move on your foot. The harder it is pressed against the skin the quicker it will generate heat and skin damage so now I wear my shoes looser. 'But Lee, won't that lead to more falls, to rolling your ankles, to your shoes falling off?' I like stretch bungee laces not only because they prevent me from having to trust in my ability to tie my shoes but also because they have give while still keeping your shoe on your foot. In an ultra my feet may swell a little over the course of the race. Almost everyone's do. I may not notice very quickly or may not want to bend down late in the race to retie my shoes laces (who knows what's going through my head then, but certainly not squatting down and standing back up). What about a looser shoe making me fall? If its so loose it can fall off then its too loose. If loosening your shoe laces or going up just a half size makes you fall on the trails then it is likely that your ankles are weak and that you also are not actually setting your feet down flat (the nervous system can lie to you about this, a blog next month on that topic). Do lunges with your eyes closed. Do single leg toe raises. Will deep mud suck a looser shoe right off my foot? It's happened. Twice. It was still lots better than running with blisters and the people running with me had a good laugh as I yelped and hopped around so it was a win-win. The key thing here I think is to experiment on training runs and see how your feet feel.
2) Socks matter a whole lot. I wore cotton socks once. They ate my feet. Some of the cheaper synthetics do too. I like Smartwool, Bridgedale, Balega, and Merrell to name a few. There are other brands that are similar and good. I hear a lot of people find happiness with drymax. For me a thicker sock is better than a thinner one. The main reason as far as I can tell is that the shoe rubs the sock and there's enough sock there to keep the rubbing from getting through to my skin. All of these socks perform just as well for me wet as they do dry. If a thicker running sock makes your shoes too tight consider a shoe with a wider toe box or a half size increase in shoe size.
3) Lubricating your feet for ultras is a great plan. I don't bother on training runs because I'm trying to toughen my feet up but training runs aren't generally as long and fast as races either. What and how much lubrication do I use? I'm not that picky with the rest of my body, though I really like Body Glide. For my feet, for an ultra? Skin Sake. Its A&D ointment with some other stuff thrown in and is much thicker on the skin than anything else I've tried, even vaseline. How much? I coat both feet everywhere my sock covers. If its the right amount then when I put on my sock and shoe it feels a little bit uncomfortably squishy for the first half mile or so. I ran an 80 mile mountain race over summer and a 100 miler in September and both involved a lot of water. I didn't get any blisters at all. Seriously.
4) Wet feet are actually good for me. When I wore my shoes tighter wet feet meant more blisters. With thicker, high quality running socks of the sort mentioned above and with lubrication on the feet (and even without, though the skin sake seems to also keep my feet from turning into prunes after 20 wet hours) wetness seems to just provide extra lubrication and keep the temperature of my skin down. Surely you've notice the skin feels hot before it blisters? That a blister from running looks like a burn? Not entirely coincidental. Once I sorted out all of the above stuff I found that wet feet ceased to be a problem which is good because you never know what it will do on race day. What about water proof shoes? You can try them but expect hot feet. Also, expect that if you do have to cross a creek (I prefer courses where this is likely because that's the kind of trail race I love most) and water gets over the top of your shoe it will not drain. No fun at all. Its also possible for it to rain so much that rain gets into your shoe. Gamble all you want, if its a race I prefer to sprint right across the creek without worrying about it. At lower paces and especially in the snow a waterproof shoe may still make sense for some runners. I just wear all mountain or thick ski socks and older, slightly stretched out shoes.
5) Blisters can be dangerous. If a blister tears open and then you blister again underneath so that you have gone through most if not all of your skin then you can wind up with a situation as dangerous as a third degree burn. This has never happened to me (very happily). In this case infection can set in and spread and turn into cellulitis which can land you in the hospital on IV antibiotics and losing tissue. First, take your blisters seriously if they are broken. Keep them clean and covered. Second, if you are at all nervous about infection but not ready to seek immediate medical intervention then take a pen and draw around the blister, outlining everywhere the skin is red/angry pink. Keep checking the blister. If the redness spreads over the line you drew you need antibiotics. You need them right away. When you get to the doctor, tell them when you put the line around the redness and how quickly it spread over the line so that they will understand the problem. I hope this never happens to anyone ever but if it does, its gonna be a whole lot easier to deal with the more quickly you get it treated.