ABSTRACT Context: Giving birth is a traumatic experience for women, and if unresolved, the emotions it causes can have a lasting negative impact on mental health, including depression in the postpartum period. Depression is a prevalent mental illness that can have major repercussions, particularly after giving birth. There is evidence of postpartum depression. However, many studies have concentrated on the prevalence of postpartum depression. In middle-income countries, including Kenya, very few studies have assessed the outcome of midwife-led debriefing for the prevention of postpartum depression. Aim: The study aimed to assess the outcome of a midwife-led debriefing on postpartum depression in the Western region of Kenya. Methods: The study was a quasi-experimental design with pre and post-test assessments. The study used the postnatal register as the sampling frame. Systematic random sampling was used to identify and allocate participants to the study's intervention and control groups. The target population was women of childbearing age. The study participants were women who gave birth during the study period, of which a sample of 212 participated in the study. The 165 participants were allocated to the intervention group, while 47 participants were in the control group, based on the 22% Prevalence of Postpartum Depression (PPD). Data was collected using a structured questionnaire on demographic characteristics and the Edinburg Postpartum Depression Scale (EPDS) for assessment of postpartum depression level. Results: The study results show that midwife-led debriefing significantly reduced the symptoms of postpartum depression (t=14.672, p-value=0.003). The Odds ratio (OR= 5.41) indicated an association between the intervention of midwife-led debriefing and the outcome (Reduced symptoms of depression) as compared with the standard care. The coefficient of β=0.871 shows a proportional shift in postpartum depression prevention of 0.871 units for every unit increase in midwife-led debriefing. At the 5% significance level, the null hypothesis was rejected (p=0.003), suggesting that postpartum depression could potentially be prevented using midwife-led debriefing. Conclusion: Midwife-led debriefing reduces postpartum depression symptoms. The study recommends that the national and county government health systems integrate midwife-led debriefing into the standard practice for postpartum care.