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Non-traumatic coma (NTC) is a common medical condition often associated with poor outcomes. Identifying underlying causes is crucial for effective management and prognostication, particularly in resource-poor settings. This study aimed to identify the most common causes and prognostic factors of NTC in a tertiary hospital in Bukavu, in the eastern Democratic Republic of the Congo (DRC), using the Glasgow Coma Scale (GCS) as well as other simple and affordable clinical and paraclinical tools. This retrospective observational study included 219 consecutive patients admitted to the intensive care unit of the Provincial General Hospital of Bukavu between January 2016 and December 2018. Sociodemographic, clinical, and laboratory data were also collected. Bivariate and multivariate analyses were performed to identify different causes and factors associated with poor outcomes in these patients. The median age of the patients was 49 (interquartile range [IQR]: 33–61) years, and they were predominantly men (62.8%). The most common causes of NTC were stroke (25.7%), acute metabolic complications of diabetes (21.9%), and primary brain infections (meningoencephalitis, 16.0%; and cerebral malaria, 14.2%). The NTC-related in-hospital mortality rate was 35.2%. A high mortality was significantly and independently associated with a GCS