Background. Drug-drug interactions (DDIs) are a common issue that leads to adverse drug reactions in hospitals. Patients in the surgical department are expected to have potential DDIs that may lead to morbidity and mortality. Objectives. To study potential DDI prevalence in the surgery departments in 3 hospitals in Palestine. Moreover, to identify pertinent factors that are associated with drug-drug interactions. Method. A cross-sectional study in 3 governmental Palestinian hospitals: Palestine Medical Complex, Rafidia Hospital, and Beit Jala Hospital. Patients who are 20 years old or above and admitted to the surgical wards between September 2017 and February 2018 were included in the study. Patient demographics, all medications given in the hospital, and hospitalization period were obtained from medical files. The digital clinical decision support system Micromedex® was used for analysis and classification of possible drug interactions. Bivariate analysis and logistic regression were used to study the risk factors for developing DDIs. Results. 502 patients were included in this report. The prevalence of potential DDIs among patients admitted to surgery wards in three Palestinian hospitals was 56%. The number of detected potential DDIs per patient was 2.22±3.76. The number of prescribed medications (P<0.001) was found to increase the possibility of having drug interactions. Conclusions. DDIs in Palestinian hospitals are a prevalent problem, and caution should be taken when ordering medications to hospitalized patients in surgery departments.