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. 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. 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. 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.