OBJECTIVE: To determine factors associated with in-hospital death among patients admitted to ICU and to evaluate the predictive values of single severely deranged vital signs and several severity scoring systems. METHODS: A combined retrospective and prospective cohort study of patients admitted to the adult ICU in a tertiary hospital in Malawi was conducted between January 2017 and July 2019. Predefined potential risk factors for in-hospital death were studied with univariable and multivariable logistic regression models, and the performance of severity scores was assessed. RESULTS: The median age of the 822 participants was 31 years (IQR 21-43), and 50% were female. Several factors at admission were associated with in-hospital mortality: the presence of one or more severely deranged vital signs, adjusted odds ratio (aOR) 1.9 (1.4-2.6); treatment with vasopressor aOR 2.3 (1.6-3.4); received cardiopulmonary resuscitation aOR 1.7 (1.2-2.6) and treatment with mechanical ventilation aOR 1.5 (1.1-2.1). Having had surgery had a negative association with in-hospital mortality aOR 0.5 (0.4-0.7). The predictive accuracy of the severity scoring systems had varying sensitivities and specificities, but none were sufficiently accurate to be clinically useful. CONCLUSIONS: In conclusion, the presence of one or more severely deranged vital sign in patients admitted to ICU may be useful as a simple marker of an increased risk of in-hospital death.