Objective: To evaluate the performance of a continuous quality improvement collaboration at Ridge Regional Hospital, Accra, Ghana, that aimed to halve maternal and neonatal deaths. Methods: In a quasi-experimental, pre-and post-intervention analysis, system deficiencies were analyzed and 97 improvement activities were implemented from January 2007 to December 2011. Data were collected on outcomes and implementation rates of improvement activities. Severity-adjustment models were used to calculate counterfactual mortality ratios. Regression analysis was used to determine the association between improvement activities, staffing, and maternal mortality. Results: Maternal mortality decreased by 22.4% between 2007 and 2011, from 496 to 385 per 100 000 deliveries, despite a 50% increase in deliveries and five-and three-fold increases in the proportion of pregnancies complicated by obstetric hemorrhage and hypertensive disorders of pregnancy, respectively. Case fatality rates for obstetric hemorrhage and hypertensive disorders of pregnancy decreased from 14.8% to 1.6% and 3.1% to 1.1%, respectively. The mean implementation score was 68% for the 97 improvement processes. Overall, 43 maternal deaths were prevented by the intervention; however, risk severity-adjustment models indicated that an even greater number of deaths was averted. Mortality reduction was correlated with 26 continuous quality improvement activities, and with the number of anesthesia nurses and labor midwives. Conclusion: The implementation of quality improvement activities was closely correlated with improved maternal mortality.