Disease processes that frequently require emergency care constitute approximately 50% of the total disease burden in low-income and middle-income countries (LMICs). Many LMICs continue to deal with emergencies caused by communicable disease states such as pneumonia, diarrhoea, malaria and meningitis, while also experiencing a marked increase in non-communicable diseases, such as cardiovascular diseases, diabetes mellitus and trauma. For many of these states, emergency care interventions have been developed through research in high-income countries (HICs) and advances in care have been achieved. However, in LMICs, clinical research, especially interventional trials, in emergency care are rare. Furthermore, there exists minimal research on the emergency management of diseases, which are rarely encountered in HICs but impact the majority of LMIC populations. This paper explores challenges in conducting clinical research in patients with emergency conditions in LMICs, identifies examples of successful clinical research and highlights the system, individual and study design characteristics that made such research possible in LMICs. Derived from the available literature, a focused list of high impact research considerations are put forth.