This retrospective study investigated the impact of foot-and-mouth disease (FMD) on productive and reproductive traits, economic losses and culling trends in Holstein cows in Iran. Data from nine industrial and semi-industrial dairy herds from several provinces were analyzed over a decade (2009-2019) and included a total of 49,400 records from 20,330 cows. A mixed linear model was used to assess the impact of FMD on milk production, fat and protein yields and reproductive traits. Information on milk production was collected over a period of 305 d. A simulated bioeconomic model was used to estimate the financial losses due to FMD incidence on productive and reproductive traits. The model included losses due to reduced milk production, discarded milk, reproductive inefficiency, morbidity, culling and replacement animals, loss of body weight, vaccination, medication and supplementation costs, and labor costs. FMD significantly reduced milk production, with an average decrease of 845.9 kg of fat corrected milk (FCM) per cow, a decrease of 44.1 kg in fat yield and a decrease of 2.3 kg in protein yield. Reproductive performance was negatively affected, with an increase in calving interval (+30.9 day), days open (+13.7 day), number of inseminations (+0.2-fold) and length of gestation (+1 day). Economic analysis showed an average loss of 082.3 per FMD case, with the highest costs attributable to culling and replacement of animals (27 %, 96.2) and reproductive inefficiency (22 %, 39.6). These results have significant implications for farm management strategies to control the spread of FMD and to plan preventative measures to reduce economic losses.