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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 duration of the study at the Armed Forces Hospital Southern Region in Khamis Mushait, Saudi Arabia, 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 DOACs 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 DOAC utilization parameters were not implemented. The results of the study provide specific improvement areas and objectives for Anticoagulation stewardship programs. [ABSTRACT FROM AUTHOR]