Febrile illnesses are a major cause of mortality in sub-Saharan Africa. Early identification of patients at increased risk of death may avert adverse outcomes. We aimed to independently evaluate the performance of the Modified Early Warning Score, quick Sequential Organ Failure Assessment (qSOFA) score, and Integrated Management of Adolescent and Adult Illness (IMAI) emergency signs and severity criteria to predict in-hospital mortality among a prospective cohort of febrile patients in Tanzania. We evaluated 419 patients aged ≥ 10 years in the period 2007-2008. Of the 44 patients who died, 31 (70.5%) were human immunodeficiency virus (HIV) infected. On univariate analysis, in-hospital mortality was associated with HIV infection, oxygen saturation < 90%, respiratory distress, Glasgow Coma Scale < 15, neck stiffness, unconsciousness, convulsions, hemoglobin < 9 g/dL, absence of a systemic syndrome, and neurologic syndrome. A qSOFA score ≥ 2, the presence of at least one, two, or three IMAI emergency signs, and IMAI severe respiratory distress syndrome without shock were significantly associated with in-hospital mortality. The criterion "presence of at least one IMAI emergency sign" showed a good diagnostic accuracy, as highlighted by the high sensitivity, low negative likelihood ratio, and wide area under the receiver operating characteristics curve. The remaining scores showed a poor performance in predicting fatal outcomes in our study population. Further studies are needed to validate our findings and to derive early warning scores that have good clinical performance in settings throughout sub-Saharan Africa.