Surgical site infection (SSI) rates in low- and middle-income countries (LMICs) range from 8 to 30% of procedures, making them the most frequent healthcare-acquired infection (HAI) with substantial morbidity, mortality, and economic impacts. Presented here is an approach to surgical site infection prevention based on surveillance and focused on five critical areas identified by international experts. These five areas include1. Collecting valid, high-quality data;2. Linking HAIs to economic incapacity, underscoring the need to prioritize infection prevention activities;3. Implementing SSI surveillance within infection prevention and control (IPC) programs to enact structural changes, develop procedural skills, and alter healthcare worker behaviors;4. Prioritizing IPC training for healthcare workers in LMICs to conduct broad-based surveillance and to develop and implement locally applicable IPC programs; and5. Developing a highly accurate and objective international system for defining SSIs, which can be translated globally in a straightforward manner.Finally, we present a clear, unambiguous framework for successful SSI guideline implementation that supports developing sustainable IPC programs in LMICs. This entails1. Identifying index operations for targeted surveillance;2. Identifying IPC “champions” and empowering healthcare workers;3. Using multimodal improvement measures;4. Positioning hand hygiene programs as the basis for IPC initiatives;5. Use of telecommunication devices for surveillance and healthcare outcome follow-ups.Additionally, special considerations for pediatric SSIs, antimicrobial resistance development, and antibiotic stewardship programs are addressed.