Background: The number of cases and mortality rates of Leptospirosis incidences in Klaten Regency is increasing from year to year. The study aims to analyze the environmental risk factors toward Leptospirosis incidences in Klaten Regency, Central Java, Indonesia. Subjects and Method: This was a case-control study conducted in Klaten Regency, Central Java. The study sample was all Leptospirosis patients who were recorded in Klaten Health Office. The case population was a total of 39 people and the control population was a total of 171 people. The dependent variable was: Leptospirosis incidences and the independent variables were physical condition of the house, environmental condition of the settlement, the presence of mice, the presence of cattle, adjacent to a river, flooding area, age, sex category, and occupation. The study instruments used were questionnaires and checklist. The data were analyzed by path analysis. Results: The risk of Leptospirosis was directly increased by the presence of mice (b= 7.34; 95% CI= 4.44 to 10.24; p<0.001) and flooding area (b= 8.99; 95% CI= 5.02 to 12.96; p <0.001). The risk of Leptospirosis was directly decreased by age ≥20 to <60 years (b= -1.45; 95% CI= -3.68 to 0.79; p=0.205) and female sex (b= -2.97; 95% CI= -5.52 to -0.42; p= 0.022). The risk of Leptospirosis was indirectly affected by the presence of mice, presence of cattle, flooding area, poor settlement condition, and poor house physical condition through area adjacent to a river, and poor physical condition of the house, working in the wet area. Conclusion: The risk of Leptospirosis is directly increased by the presence of mice and flooding area. The risk of Leptospirosis is directly decreased by age ≥20 to <60 years and female sex. The risk of Leptospirosis is indirectly affected by the presence of mice, presence of cattle, flooding area, poor settlement condition, and poor house physical condition through area adjacent to a river, and poor physical condition of the house, working in the wet area Keyword s : Leptospirosis, environmental risk factors, path analysis Correspondence: Patria Sari Dewi. Public Health Office (Balkesmas) of Klaten, Central Java. Email: patriaklaten@gmail.com. Phone: 085643157125. Journal of Epidemiology and Public Health (2020), 05(02): 158-167 https://doi.org/10.26911/jepublichealth.2020.05.02.04