Introduction: The US Marines operate the Jungle Warfare Training Center (JWTC) in Northern Okinawa, where leptospirosis is endemic. The JWTC endurance course involves prolonged fresh and stagnant water exposures in a simulated jungle warfare environment. Since a leptospirosis outbreak in 1987, JWTC has required prophylactic use of doxycycline at 200 mg weekly during exposure to the endurance course. This policy is based on a 1982 study in a similar environment in Panama. In August and September of 2014, an outbreak of leptospirosis occurred among 81 Marines training at JWTC. We analyzed data from the largest reported outbreak of leptospirosis among US military members. Materials and Methods: Two hundred and thirty nine US Marines who completed the endurance course were interviewed by trained personnel regarding their exposures and use of prophylactic medication utilizing a standardized questionnaire. All available personnel who went through the course during the outbreak period were interviewed regardless of whether or not they became ill. The Armed Forces Health Surveillance Branch's case definition was used to identify cases. Results: Eighty-one cases in 239 personnel were identified (attack rate = 33.9%). Exposures linked to being a case were swallowing water in the stagnant pond (attack rate ratio [ARR] = 2.3, 95% confidence interval [CI] = 1.4-3.7), cuts on the body (ARR = 1.5, 95% CI = 1.01-2.11), and insect bites (ARR = 2.0, 95% CI = 1.2-3.4). Exposures not linked to being a case were taking doxycycline before the exposure (ARR = 3.2, 95% CI = 0.5-22.2), taking doxycycline after the exposure (ARR = 0.9, 95% CI = 0.6-1.3), and swallowing water in the natural stream (ARR = 1.3, 95% CI = 0.9-1.9). Conclusions: Attack rate data indicate that whether or not personnel took pre- or post-exposure doxycycline made no difference statistically. Increased internal exposure (via swallowing water or through broken skin) increased risk of symptomatic disease. This new study combined with a growing body of literature should prompt researchers to re-examine recommendations for those with significant water exposure in areas with high leptospirosis levels.