Leptospirosis, a bacterial zoonosis that primarily affects tropical regions, is one of the neglected diseases of the Global South, particularly in Latin America and the Caribbean: its actual incidence and case-fatality rate are uncertain, with the latter likely being high. However, its public health impact in the French West Indies was known to be significantly greater than that of the disease in mainland France, but the epidemiological indicators on which this assessment was based lacked reliability and precision. An incidence study was conducted in the French West Indies in 2011 using all currently available diagnostic tools, notably PCR. The incidence of leptospirosis was estimated at 69 and 61 cases per 100,000 inhabitants per year in mainland Guadeloupe and Martinique, respectively—an incidence more than 100 times higher than that in mainland France. The epidemiology of the disease was also characterized in terms of severity, demographic characteristics, and seasonality. These results show that access to PCR-based diagnosis leads to a number of cases in the French West Indies that is significantly higher than previously reported. This test also allows for early diagnosis of the disease, thereby limiting the risk of leptospirosis complications through the prescription of antibiotic treatment. The use of these diagnostic tests, generally recommended by the French National Authority for Health in the early stages of the disease, is of particular importance in the French West Indies. These results also confirm the relevance of establishing an epidemiological surveillance system designed to provide early warning, closely integrated with a strategy for the prevention and control of the disease. (R.A.)