BACKGROUND Leptospirosis is emerging as one of the growing public health problems in many parts of India. It can occur in both rural and urban areas with varied risk factors. This study was taken up in three districts of Maharashtra namely-Mumbai, Ratnagiri, and Sindhudurg to understand the determinants of leptospirosis in both the urban and rural areas and look for differences if any. METHODS This cross-sectional study was carried out during the year 2017. A pretested validated questionnaire was used to collect data. Field observations were made. Eighty-seven cases from Sindhudurg and 14 from Ratnagiri and 307 cases from Mumbai were included in the study. RESULTS A total of 408 cases were included in the study. A total of 63 (62.4%) were males and 38 (37.6%) were females. Most cases belonged to the 20-35 year age group (37%). In rural areas, 32.7% of them visited government facilities first, whereas, in the urban areas, it was 73.9% (P = 0.006). Headache, myalgia, and prostration were more common in cases from rural areas (P = <0.05). Skin rash was found to be associated with urban cases of leptospirosis. The presence of rodents, cattle sheds, pets, and working in paddy fields were common environmental risks in rural areas, and using water for recreational activities were common in urban areas (P < 0.001). CONCLUSIONS Context-specific risk factors were found significantly associated with the cases. No important difference was found in the epidemiology of leptospirosis in the urban and rural areas except the source of infection.