Background Providing compensation for participants in clinical research is well established and while international guidelines exist, defining a context-specific and fair compensation for participants in low-resource settings is challenging due to ethical concerns and the lack of practical, national compensation and reimbursement frameworks. Methods We reviewed Oxford University Clinical Research Unit (OUCRU) internal reimbursement documentation over a 10-y period and conducted a scoping literature review to expand our knowledge of compensation and reimbursement practices including ethical concerns. We developed a preliminary reimbursement framework that was presented to community advisory boards (CAB) and clinical investigators to assess its applicability, fairness and transparency. Results The main topics discussed at the workshops centered on fairness and whether the reimbursements could be perceived as financial incentives. Other decisive factors in the decision-making process were altruism and the loss of caregivers’ earnings. Investigators raised the issue of additional burdens, whereas the CAB members were focused on non-monetary elements such as the healthcare quality the patients would receive. All elements discussed were reviewed and, where possible, incorporated into the final framework. Conclusion Our new reimbursement framework provides a consistent, fair and transparent decision-making process and will be implemented across all future OUCRU clinical research in Vietnam.