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Abstract Background Vaccine wastage undermines the cost-effectiveness of immunization programs, especially in resource-constrained settings. However, data on vaccine wastage in Uganda are limited. We assessed the magnitude of vaccine wastage, its causes, and associated factors in Rukungiri District, South-western Uganda. Methods In a cross-sectional mixed-methods study, we analyzed data from the District Health Information Systems database and immunization program records at health facilities in Rukungiri District for July 2018–June 2019. Wastage rates were calculated as the proportion of vaccine doses wasted after an immunization session, expressed as a percentage of the total doses opened. Chi-square or Fischer’s exact tests were used to examine the association between wastage and various factors. Qualitative data were collected through in-depth interviews with health workers involved in immunization activities and analyzed thematically. Results Vaccine wastage rates varied across different vaccines, with BCG at 81.1%, OPV at 31.6%, IPV at 31.3%, DPT-HepB-Hib at 20.0%, PCV-10 at 10.2%, MCV at 57.7%, and Rota virus vaccine at 2.1%. The main cause of wastage was discarding leftover doses. For BCG, larger health facilities had significantly lower wastage than smaller ones (Hospital 66.0%, HCIV 74.3%, HCIII 80.6%,HCII 87.0%, p = 0.005), facilities with predominantly small session sizes had higher wastage rates than those with mixed or large session sizes (84.4%vs64.3%vs62.0%p < 0.01) and fewer static sessions per month were associated with higher wastage (82.1%vs 66.0%p = 0.013). Good coverage was linked to lower wastage for DPT-HepB-Hib and PCV-10 (DPT-HepB-Hib 16.8% vs 31.2%p = 0.033 PCV-10 9.1%vs13.7%p = 0.001). Freeze-dried vaccines had a substantially higher wastage rate of 75.0% compared to liquid vaccines at 20.2% (p < 0.01). Injectable vaccines had a higher wastage rate (47.1%) than oral vaccines (22.6%, p < 0.01). Larger vial sizes were also associated with higher wastage rates. Knowledge and skills gaps were identified in stock and cold chain management practices. Conclusion Wastage rates for several vaccines exceeded national limits, primarily due to discarding leftover doses. Factors like vaccine type, administration method, vial size, and facility size influenced wastage. Targeted strategies, including stock management improvements and health worker training, could enhance immunization program cost-effectiveness and sustainability in the region
Kemigisha et al. (Tue,) studied this question.