Purpose: Leptospirosis is a major public health problem in tropical countries with potentially fatal systemic complications and multi-organ dysfunction. Leptospirosis is endemic in Bantul area. This study aimed to identify the major risk of the factors which contribute to the mortality of leptospirosis patient in Bantul area during 2012-May 2017. Methods: This study using case-control study design with ratio 1:3, 32 cases and 96 controls. The collected data were the manifestation of clinic and laboratory findings from the medical records of leptospirosis patient during 2012-May 2017 in Bantul District Hospital. The inclusion criteria in this study was based on pertinent clinical and epidemiological data and positive serology, patient who domiciled and living in Bantul District Area. The data were analyzed using Fisher test, Chi-square, and multiple logistic regression. The data processed using STATA Software version 13.1. Results: A total of 128 patients were included, with mean age 50.9±12.5 years; 75% (n=96) were male. The mean length from onset symptoms to admission was 4.5±2.27 days. Multivariate logistic regression demonstrated that four dominant factors were significantly independent associated with mortality, icteric, myalgia, dyspnea and thrombocytopenia. Conclusion: The presence of dyspnea, myalgia, icterus, and thrombocytopenia (<100.000/µL) on admission in patients with leptospirosis indicated high risk of death.