District hospitals in Uganda face challenges in cost-effectiveness due to inefficient systems. A mixed-method approach combining quantitative data from financial audits and qualitative insights from healthcare staff interviews was employed. District hospitals incurred an average of $12,000 per month in operational costs, with significant variability across districts (e.g., variance = $5,000). The quasi-experimental design revealed disparities in system efficiency and cost management among district hospitals. Strategic investments are recommended to enhance resource allocation and streamline operations for improved cost-effectiveness. District Hospitals, Quasi-Experimental Design, Cost-Effectiveness Analysis, Uganda