Background: Global health programmes require extensive adaptation for implementation in conflict and post-conflict settings. Without such adaptations, both implementation success and diplomatic, international relations and other indirect outcomes may be threatened. Conversely, diplomatic successes may be made through flexible and responsive programmes. We examine adaptations and associated outcomes for malaria treatment and prevention programmes in Afghanistan. Methods: In conjunction with the completion of monitoring and evaluation activities for the Global Fund to Fight AIDS, Tuberculosis and Malaria, we reviewed adaptations to the structure, design, selection, content and delivery of malaria-related interventions in Afghanistan. Interviews were conducted with programme implementers, service delivery providers, government representatives and local stakeholders, and site visits to service delivery points were completed. Findings: Programmes for malaria treatment and prevention require a range of adaptations for successful implementation in Afghanistan. These include (1) amendment of educational materials for rural populations, (2) religious awareness in gender groupings for health educational interventions, (3) recruitment of local staff, educated in languages and customs, for both quality assurance and service delivery, (4) alignment with diplomatic principles and, thereby, avoidance of confusion with broader strategic and military initiatives and (5) amendments to programme ‘branding’ procedures. The absence of provision for these adaptations made service delivery excessively challenging and increased the risk of tension between narrow programmatic and broader diplomatic goals. Conversely, adapted global health programmes displayed a unique capacity to access potentially extremist populations and groups in remote regions otherwise isolated from international activities. Conclusions: A range of diplomatic considerations when delivering global health programmes in conflict and post-conflict settings are required in order to ensure that health gains are not offset by broader international relations losses through challenges to local cultural, religious and social norms, as well as in order to ensure the security of programme staff. Conversely, when global health programmes are delivered with international relations considerations in mind, they have the potential to generate unquantified diplomatic outcomes.