There are many causes of blisters, including: 1  Irritation — Blisters can be caused by physical factors that irritate the skin, such as friction (rubbing the skin), irritating chemicals or extreme cold or heat. Blisters on the feet can result from shoes that are either too tight or rub the skin in one particular area. Blisters also can be caused by contact dermatitis, a skin reaction to some type of chemical irritant. Intense cold can trigger frostbite, which often leads to blisters once the skin is rewarmed.