Health workforces across all levels of the healthcare system are the main modulators in the effective implementation of disease surveillance system. However, their level of integrated disease surveillance response (IDSR) practice and determinant factors was hardly investigated in Ethiopia. This study determined the level of IDSR practice and associated factors among health professionals in the west Hararghe zone, eastern Oromia, Ethiopia. Methodology: A multicenter facility-based cross-sectional study design was conducted between December 20, 2021, and January 10, 2022, among 297 systematically selected health professionals. Trained data collectors collected data using structured pretested selfadministered questionnaires. The level of IDSR practice was assessed using six questions where each acceptable practice was given "1" and unacceptable "0", with a total score of 0 to 6. Hence, a score above or equal to the median was categorized as good practice. Epi-data and STATA were used for data entry and analysis. A binary logistic regression analysis model with an adjusted odds ratio was used to determine the effects of independent variables on the outcome variable.