Surgical site infections (SSIs) are a major problem in developing countries, with prevention measures often poorly implemented. A study of four African hospitals aimed to establish the impact of a multimodal intervention to address SSIs. The intervention involved implementing or strengthening a range of prevention measures and promoting an adaptive approach to improve safety and teamwork. The before-after cohort study covering 4,322 operations showed a significant decrease in SSI outcome, from 8% to 3.8%, and a sizable improvement in adherence to prevention measures. The likelihood of SSI was significantly lower post-intervention, but there was no significant reduction in death rates.