Background: After delivery psychological disorder otherwise appropriately and immediately handled may lead to postpartum depression (PPD). PPD has serious impact on mothers that manifests as lower quality of life and inability to care of themselves, their partner, and infants. There is a lack of studies on PPD in Indonesia. Its prevalence and determinants are not wellunderstood. This study seek to estimate the prevalence and the determinants of PPD in Sukoharjo, Central Java. Subjects and Method: This was an analytic observational study with cross-sectional design. The study was conducted at community health centers in Sukoharjo District, Central Java, from November to December, 2017. A total sample of 200 postpartum mothers was selected for this study using cluster random sampling, with community health center as the cluster. The dependent variable was PPD. The independent variables were maternal age, parity, labor complication, maternal education, self-efficacy, family income, coping strategy, unwanted pregnancy, and family support. The data were collected by questionnaire and analyzed by path analysis. Results: PPD prevalence in Sukoharjo, Central Java, was 18.5%. The risk of PPD increased with labor complication (b= 3.14, SE= 0.45, p<0.001), unwanted pregnancy (b= 1.54, SE= 0.45, p<0.001), and low family income (b= -0.05, SE= 0.01, p<0.001). The risk of PPD decreased with age (b= -0.07, SE= 0.03, p= 0.028), stronger self-efficacy (b= -0.55, SE= 0.09, p<0.001), and improved coping strategy (b= -0.56, SE= 0.03, p= 0.064). Unwanted pregnancy increased with younger age (b= -0.02, SE= 0.01, p= <0.001), parity (b= 0.27, SE= 0.04, p<0.001), weaker family support (b= -0.05, SE= 0.02, p= 0.044), and lower family income (b= -0.01, SE= <0.01, p= 0.003). The risk of labor complication decreased with increasing age (b= -0.03, SE= 0.01, p<0.001) and higher family income (b= -0.01, SE= <0.01, p<0.001), but increased with parity (b= 0.27, SE= 0.05, p<0.001). Coping strategy improved with increasing age (b= 0.17, SE= 0.07, p= 0.015) and higher maternal education (b= 1.94, SE= 0.48, p<0.001). Self-efficacy increased with higher family income (b= 0.04, SE= 0.01, p<0.001) and stronger family support (b= 0.03, SE= 0.12, p= 0.016). Conclusion: PPD prevalence is 18.5% in Sukoharjo, Central Java. The risk of PPD increases with labor complication, unwanted pregnancy, and low family income, but decreases with age, stronger self-efficacy, and improved coping strategy.