Background: Salmonella typhi infection causes a significant amount of morbidity and mortality worldwide. Most typhoid suspected patients do not have access to a proper laboratory diagnosis as the necessary facilities are often lacking in developing countries like Ethiopia. Objectives: The aim of this study was to evaluate the performance of Enterocheck WB test and Widal test considering stool culture as gold standard in the laboratory diagnosis of typhoid fever. Materials and Methods: Two-hundred seventy typhoid suspected patients at Hawassa University Comprehensive Specialized Hospital from June 2022 to September 2022 were included in this cross-sectional study. Descriptive statistics were used to summarize the data. Sensitivity, specificity, positive and negative predictive values were determined for Enterocheck WB test and Widal test. Kappa value was used to analyze the result agreement. A statistical package for social sciences (IBM SPSS version 23) was used for the analysis of the data and the p ≤ 0.05 was taken as significant. Result: Sensitivity, specificity, positive, and negative predictive values of Enterocheck WB test were 70%, 99.2%, 77.8%, and 98.9% respectively. For Widal qualitative agglutination sensitivity, specificity, positive and negative predictive values were 100%, 56.5%, 8.1%, and 100% respectively. Widal semi-quantitative agglutination had sensitivity, specificity, Positive, and negative predictive values of 90%, 62.31%, 8.41%, and 99.4%, respectively. Enterocheck WB was almost in perfect agreement with the stool culture (kappa = 0.737, p = 0.001) while Widal qualitative and Widal semi-quantitative agglutination had a poor agreement with the stool culture (kappa = 0.08, p = 0.001) and (kappa = 0.09, p = 0.001) respectively. Conclusions and Recommendations: Widal test has high sensitivity and negative predictive value; however, it showed low specificity and very low positive predictive value. The Widal test might not be reliable for the diagnosis of typhoid fever as false positives are common. Enterocheck WB had low sensitivity but showed high specificity, positive predictive value, and negative predictive value. The performance of Enterocheck WB was better than the Widal test when compared with the stool culture. Therefore, Enterocheck WB would be used as a rapid diagnostic method in the investigation of typhoid fever where culture facilities are not available