The purpose of this systematic review was to determine if sock, antiperspirant, or barrier strategies were effective in prevention of friction blisters in wilderness and outdoor pursuits. A search of PubMed and EMBASE was conducted. Title, abstract, and full text articles were screened by 2 authors using predetermined inclusion and exclusion criteria to identify prospective controlled trials investigating prevention methods for friction blisters involving the foot. Only blisters associated with wilderness and outdoor pursuits (running, hiking, marching, etc.) were considered. Extraction of a predetermined data set was accomplished using a piloted form. Confidence in effect estimates were determined utilizing the Scottish Intercollegiate Guidelines Network methodology checklist. Literature search resulted in 806 discrete articles. After screening, 11 studies were identified for inclusion in systematic review. Included studies investigated 5 sock, 3 antiperspirant, and 3 barrier strategies. Only 2 articles were determined to have moderate confidence in effect estimate. Clinical and methodologic diversity precluded meta-analysis. Despite the high frequency, discomfort, and associated cost there is a paucity of high-quality quality evidence in support of socks, antiperspirants, or barriers for the prevention of friction blisters. Moderate confidence in effect estimate suggests that paper tape may be an effective form of barrier prevention.