District hospitals in Ghana play a crucial role in healthcare provision, yet their effectiveness varies significantly across different regions. A longitudinal study using mixed-methods approach including surveys, interviews, and financial data analysis to assess system performance over time. District hospitals in the Northern Region showed an average reduction of 20% in patient wait times compared to Southern Region (p<0.05), indicating variability in service delivery quality. Quasi-experimental design proved effective for measuring cost-effectiveness, with specific findings highlighting regional disparities. Targeted interventions should be developed based on identified system inefficiencies and strengths. district hospitals, cost-effectiveness, quasi-experimental design, Ghana Treatment effect was estimated with $\text{logit}(p_i)=\beta_0+\beta^\top X_i$, and uncertainty reported using confidence-interval based inference.