OBJECTIVE: This study aimed to assess the appropriateness of direct oral anticoagulants (DOACs) utilization in a Saudi tertiary hospital. PATIENTS AND METHODS: Adult inpatients and outpatients diagnosed with atrial fibrillation, deep vein thrombosis, or pulmonary embolism were included in a retrospective cohort study. Patients received at least one month of apixaban, rivaroxaban, or dabigatran. The dura-tion of the study at the Armed Forces Hospital Southern Region in Khamis Mushait, Saudi Ara-bia, was from January 1, 2019, to December 31, 2021. The study assessed the appropriateness of DOACs dosing, initial and follow-up monitoring, the presence of clinically significant interactions, and treatment duration adherence.RESULTS: 778 patients were included in the analysis (mean age 71.34 +/- 15.98 years, equal male and female representation). Rivaroxaban was administered to 40.8% of the patients, while apixaban and dabigatran were administered to 31.02% and 28.18% of the patients, respectively. The most prevalent indication for DO-ACs was atrial fibrillation (72.84%), followed by deep vein thrombosis and pulmonary embolism (27.16%). The most prevalent category of medication errors was inappropriate maintenance dose (41.7%), followed by inappropriate initial dose (37.97%) and lack of laboratory parameter monitoring (36.42%). 31.5 percent of the study sample lacked baseline renal functions, while 24.5% of patients lacked baseline liver functions. 115 patients (14.8%) had potential clinically significant interactions. Regarding treatment duration, 232 patients (29.8%) were improperly prescribed DOACs based on their indications.CONCLUSIONS: In a significant proportion of DOAC patients, the prescribed rational DO -AC utilization parameters were not implement-ed. The results of the study provide specific improvement areas and objectives for Anticoagulation stewardship programs.