Abstract Background The National Institute for Health Research Global Health Research Unit on Global Surgery is establishing research Hubs in low- and middle-income countries (LMICs). The aim of this study was for the Hubs to prioritize future research into areas of unmet clinical need for patients in LMICs requiring surgery. Methods A modified Delphi process was overseen by the research Hub leads and engaged LMIC clinicians, patients and expert methodologists. A four-stage iterative process was delivered to prioritize research topics. This included anonymous electronic voting, teleconference discussions and a 2-day priority-setting workshop. Results In stage 1, Hub leads proposed 32 topics across six domains: access to surgery, cancer, perioperative care, research methods, acute care surgery and communicable disease. In stages 2 and 3, 40 LMICs and 20 high-income countries participated in online voting, leading to identification of three priority research topics: access to surgery; outcomes of cancer surgery; and perioperative care. During stage 4, specific research plans to address each topic were developed by Hub leads at a priority-setting workshop. Conclusion This process identified three priority areas for future research relevant to surgery in LMICs. It was driven by front-line LMIC clinicians, patients and other stakeholders representing a diverse range of settings. The results of the prioritization exercise provide a future framework for researchers and funders.