Post-discharge death is increasingly recognized as an important contributor to pediatric mortality in sub-Saharan Africa. To address morbidity and mortality during this period, a representative evidence base is needed to inform resource prioritization, policy, and guideline development. To date, no studies have been conducted in Rwanda, limiting understanding of post-discharge mortality in this region. We conducted a prospective cohort study of children ages 0-60 months in two Rwandan hospitals, one rural (Ruhengeri) and one urban (Kigali), from May 2022 to February 2023. We collected clinical, laboratory, and sociodemographic data on admission and follow-up data on vital statistics at 2-, 4-, and 6-months post-discharge. Of 1218 children enrolled, 115 (9.4%) died, with half occurring in-hospital (n=57, 4.7%) and half after discharge (n=58, 4.7%). Post-discharge mortality was lower in the 6-60-month cohort (n=30, 3.5%) than in the 0-6-month cohort (10%) and higher in Kigali (n=37, 10.3%) vs. Ruhengeri (n=21, 2.7%). Median time to post-discharge death was 38 days (IQR: 16-97.5) in the 0-6-month cohort and 33 days (IQR: 12-76) in the 6-60-month cohort. In the 0-6 months cohort, malnutrition (weight-for-age z-score <-3) was associated with increased odds of post-discharge death (aOR 3.31, 95% CI 1.28-8.04), while higher maternal education was protective (aOR 0.15, 95% CI 0.03-0.85). Significant factors associated with post-discharge death in the 6-60-month cohort included an abnormal Blantyre Coma Scale (aOR 3.28, 95% CI 1.47-7.34), travel time to care >1 hour (aOR 3.54, 95% CI 1.26-9.93), and referral for higher levels of care (aOR 4.13, 95% CI 1.05-16.27). Children aged <2 months exhibited the highest cumulative mortality risk. Post-discharge mortality among Rwandan children remains a significant burden, necessitating targeted interventions for post-discharge care and follow up to reduce mortality.