Objective.—To determine the prevalence and predictors of injury and illness among long-distance hikers.Methods.—This was a cross-sectional study of long-distance hikers (>500 miles [805 km]) along the Appalachian Trail and Pacific Crest Trails between August and October of 2006. An 8-page survey instrument was made available to hikers at a designated station near the northern terminus of the respective trails. The survey questions were yes/no or multiple choice. Independent variables included packweight, footwear, and type and frequency of water purification. χ2 tests to compare categorical data and the Cochran-Armitage test for trend were used (P < .05 significant). We used logistic regression to compare the variables concurrently, and significance was determined using likelihood ratio tests. Profile likelihood confidence intervals for the odds ratios are reported.Results.—Of the 128 hikers completing surveys that met inclusion criteria, the mean age was 33 years (range = 18–65 years), 94% walked >1500 miles (2400 km), and 70% were male. Using univariate analysis, trends were noted in the proportion of hikers reporting paresthesias and increasing packweight (35% with 10–20 pound [4.5–9 kg] packs, 50% with 21–30 pound [9.5–13.5 kg] packs, and 69% with >31 pound [14 kg] packs [P < .002]), as well as in the proportion of hikers reporting paresthesias and increasing footwear rigidity (29% sandals, 36% running shoes, 42% hiking shoes, and 68% hiking boots [P < .001]). In multivariate analysis compared to sandals, the odds ratio of suffering from paresthesias with running shoes was 1.57 (95% CI 0.3, 12.2), hiking shoes 1.73 (95% CI 0.3, 13.9), and hiking boots 3.9 (95% CI 0.7, 32.1) (P = .16). Compared to 10 to 20 pound (4.5–9 kg) packs, the odds ratios of suffering from paresthesias with 21 to 30 pound (9.5–13.5 kg) packs was 1.5 (95% CI 0.6, 3.9), and for >31 pounds (14 kg) was 2.2 (CI 0.7, 7.1) (P = .03). Adjusting for footwear and pack weight, only pack weight was significantly associated with paresthesias. Packweight and footwear were not significantly associated with other musculoskeletal injuries, such as joint sprains or chronic pain, and muscle injuries.Conclusions.—There is an association between packweight and the prevalence of paresthesias among long-distance hikers. The association between type of footwear and the prevalence of paresthesias is significant when analyzed independently, but loses its significance when the variables are examined together. This suggests that there is confounding between footwear and packweight.