The burden of stroke is increasing in developing countries that struggle to manage it efficiently. We identified determinants of early case-fatality among stroke patients in Maputo, Mozambique, to assess the impact of in-hospital complications. Patients admitted to any hospital in Maputo with a new stroke event were prospectively registered (n = 651) according to the World Health Organization's STEPwise approach, in 2005–2006. We assessed the determinants of in-hospital and 28-day fatality, independently of age, gender and education, and computed population attributable fractions. In-hospital mortality was higher among patients with Glasgow score at admission ≤6 (more than fivefold) or needing cardiopulmonary resuscitation during hospitalization (approximately 2·5-fold). Pneumonia and deep vein thrombosis/other cardiovascular complications during hospitalization were responsible for 19·6% (95% confidence interval, 5·3 to 31·7) of ischaemic stroke and 15·9% (95% confidence interval, 5·8 to 24·9) of haemorrhagic stroke deaths until the 28th day. Ischaemic stroke patients with systolic blood pressure 160–200 mmHg had lower in-hospital mortality (relative risk = 0·32, 95% confidence interval, 0·13 to 0·78), and, for those with haemorrhagic events (haemorrhagic stroke), 28-day mortality was higher when systolic blood pressure was over 200 mmHg (hazard ratio = 3·42; 95% confidence interval, 1·02 to 11·51), compared with systolic blood pressure 121–140 mmHg. Regarding diastolic blood pressure, the risk was lowest at 121–150 mmHg for ischaemic stroke and at 61–90 mmHg for haemorrhagic stroke. Early case-fatality was mostly influenced by stroke severity and in-hospital complications. The allocation of resources to the latter may have a large impact on the reduction of the burden of stroke in this setting.