Through a longitudinal, active surveillance for Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis infection and lesions on the Pacific Coast of Colombia, risk factors for infection (leishmanin skin test conversion), leishmanial lesions, and pathogenicity were examined. Risk factor information was obtained prior to and independently of case ascertainment. Similar factors were associated with acquisition of infection and of leishmaniasis, including male sex, age > 10 years, and farming occupation. The behaviors of entering the forest after sunset, hunting, and lumbering were most strongly associated with Leishmania infection independently of age, sex, and farming occupation. Environmental conditions associated with infection, including tall trees near the home, home located > 15 m from the nearest neighbor, and floor and roof made of open material, were less strong predictors of risk. Pathogenicity, the risk of lesion given a new infection, was reduced in those > 30 years of age and those entering the forest frequently.