Objective: To determine the etiologies of tropical acute febrile illness (TAFI) in West Pahang, Malaysia and to investigate morbidity and mortality factors in relation to TAFI. Methods: A multicenter prospective cohort study was conducted between January and June 2016 in six district hospitals throughout the western part of Pahang State in Peninsular Malaysia. A total of 336 patients answered a standardized questionnaire and blood samples were collected for laboratory confirmation of infectious etiology. Descriptive analysis and logistic regression were performed to identify factors associated with TAFI. Results: A total of 336 patients were included. The patients were mainly Malays (70.2%), males (61.3%), aged (44.6±17.4) years, with more than half (58.9%) presenting with gastrointestinal symptoms. The majority were diagnosed with dengue (35.7%) while malaria (4.5%) was the least frequent. The in-hospital mortality due to TAFI was 9.2%. Patients with meliodosis had five times higher mortality [Adjusted OR: 5.002, 95% CI: (1.233, 20.286)]. Patients with comorbidities such as cardiovascular symptoms (P <0.001) and renal replacement therapy initiation (P <0.001) were significantly associated with in-hospital mortality in all TAFI. Conclusions: The etiology of TAFI in the western Pahang includes dengue, leptospirosis, malaria and melioidosis, which carry the highest risk of in-hospital mortality. The presence of cardiovascular symptoms may be used to assess the disease severity in TAFI, but more studies are needed in the future.