To determine the exposure risk factors of highly endemic rural leptospirosis in tropical setting, we conducted a prospective, hospital-based case control study in Sri Lanka. A conceptual hierarchy of variables was used to analyze the data. Case patients included 38 (34%) females and 73 (66%) males with a mean age of 36 yr (SD 12.7 yr). Using piped, chlorinated water for drinking/general purposes (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.16-0.67), paddy fields in the vicinity of home (OR 1.77, 95% CI 1.06-2.97), sighting dogs at home yard/dog ownership (OR 1.79, 95% CI 1.11-2.91), sighting cattle at home yard/cattle ownership (OR 1.69, 95% CI 1.00-2.84), and work in a paddy field (OR 3.02, 95% CI 1.68, 5.41) were the main predictors of leptospirosis among febrile patients. In high endemic tropical settings with rural leptospirosis, risk factors in residential environments, rather than individual exposures, seemed to play a major role in leptospirosis disease transmission.