Leptospirosis is an epidemic-prone zoonotic disease that occurs worldwide. In Central America, leptospirosis outbreaks have been reported in almost all countries; Nicaragua in particular has faced several outbreaks. The objective of this study was to stratify the risk and identify "critical areas" for leptospirosis outbreaks in Nicaragua, and to perform an exploratory analysis of potential "drivers". This ecological study includes the entire country (153 municipalities). Cases from 2004 to 2010 were obtained from the country's health information system, demographic and socioeconomic variables from its Census, and environmental data from external sources. Criteria for risk stratification of leptospirosis were defined. Nicaragua reported 1,980 cases of leptospirosis during this period, with the highest percentage of cases (26.36%) in León, followed by Chinandega (15.35%). Among the 153 municipalities, 48 were considered critical areas, 85 were endemic and 20 silent. Using spatial and statistical analysis, the variable presenting the most evident pattern of association with critical areas defined by top quintile of incidence rate is the percentage of municipal surface occupied by the soil combination of cambisol (over pyroclastic and lava bedrock) and andosol (over a volcanic ashes foundation). Precipitation and percentage of rural population are also associated with critical areas. This methodology and findings could be used for Nicaragua's Leptospirosis Intersectoral Plan, and to identify possible risk areas in other countries with similar drivers.