Introduction: In France, vaccination against leptospirosis—limited to the Icterohemorrhagiae serogroup—is recommended for professions considered to be at risk of this infection. In 2000, the National Reference Center (CNR) for Leptospira reported an incidence of leptospirosis of 0.44 per 100,000 inhabitants, one of the highest in Western Europe. The aim of this study was to identify risk factors for leptospirosis in France in order to improve current vaccination and risk factor prevention recommendations. Methods: A matched case-control study was conducted. Cases were individuals, reported by the NRC, who had been hospitalized in France between July 1, 1999, and February 15, 2000, with fever (>/=39°C), myalgia, and a laboratory diagnosis of leptospirosis (by culture, serology, or PCR). Two controls per case were matched for sex, age group, hospital, date of hospitalization (+/-30 days), and history of hospitalization. A standardized questionnaire regarding risk factors during the three weeks preceding hospitalization was administered by telephone to all subjects by physicians from the Institute of Agricultural Medicine (INMA). Results: The questionnaire was completed for 97 cases among the 102 eligible cases identified by the CNR. The analysis was performed for 90 cases and 169 controls. A conditional logistic regression model showed that skin lesions (OR 7.0; 95% CI 2.7–17.6), canoeing and kayaking (OR 15.5; 95% CI 1.6–147.0), and contact with wild rodents (OR 4.9; 95% CI 1.4–16.2) were independently associated with leptospirosis. Conclusion: These results highlight the increase in recreational activities as risk factors for leptospirosis and the need to review leptospirosis prevention policies in France. (R.A.)