BACKGROUND: A Surgical Unit-based Safety Programme (SUSP) has been shown to improve perioperative prevention practices and to reduce surgical site infections (SSI). It is critical to understand the factors influencing the successful implementation of the SUSP approach in low- and middle-income settings. We undertook a qualitative study to assess viability, and understand facilitators and barriers to implementing the SUSP approach in 5 African hospitals. METHODS: Qualitative study based on interviews with individuals from all hospitals participating in a WHO-coordinated before-after SUSP study. The SUSP intervention consisted of a multimodal strategy including multiple SSI prevention measures combined with an adaptive approach aimed at improving teamwork and safety culture. RESULTS: Thirteen interviews (5 head surgeons, 3 surgeons, 5 nurses) were conducted with staff from five hospital sites. Identified facilitators included influential individuals (intrinsic motivation of local SUSP teams, boundary spanners, multidisciplinary engagement, active leadership support), peer-to-peer learning (hospital networking and positive deviance, benchmarking), implementation fitness (enabling infrastructures, momentum from previous projects), and timely feedback of infection rates and process indicators. Barriers (organisational 'constipators', workload, mistrust, turnover) and local solutions to these were also identified. CONCLUSIONS: Participating hospitals benefitted from the SUSP programme structures (e.g. surveillance, hospital networks, formation of multidisciplinary teams) and adaptive tools (e.g. learning from defects, executive rounds guide) to change perceptions around patient safety and improve behaviours to prevent SSI. The combination of technical and adaptive elements represents a promising approach to facilitate the introduction of evidence-based best practices and to improve safety culture through local team engagement in resource-limited settings.