BACKGROUND: Diagnostic accuracy in cases of infectious diseases is crucial for appropriate patient management and public health interventions. This retrospective study aimed to evaluate the most common causes of death caused by infectious diseases and the rate of agreement between clinical diagnoses and autopsy findings in individuals diagnosed with infectious diseases in Mashhad, Iran. METHODS: Autopsy reports from March 2009 to February 2018 were analyzed for patients diagnosed with infectious diseases. Demographic data, clinical diagnoses, and autopsy results were collected and compared. Discrepancies between clinical and autopsy diagnoses were assessed, and potential predictors of diagnostic discrepancy were examined. RESULTS: Among 28 451 autopsied cases, 546 (1.9%) were diagnosed with infectious diseases. Pleuropulmonary infections were the most common cause of death (69.8%) as determined by autopsy, followed by bloodstream infections (14.1%) and intra-abdominal infections (10.0%). Discrepancies between clinical and autopsy diagnoses were identified in 22.4% of cases. Pleuropulmonary infections had the highest frequency of diagnostic discrepancies (29.1%), followed by central nervous system (CNS) infections (15.8%). CONCLUSIONS: This study underscores the importance of autopsy in identifying diagnostic discrepancies and improving clinical practice in cases of infectious diseases. They also highlight the need for ongoing efforts to enhance diagnostic capabilities, particularly in challenging cases such as pleuropulmonary and CNS infections, to reduce the burden of misdiagnosis and improve patient outcomes.