Background: Cardiovascular diseases (CVDs) are responsible for a significant proportion of mortalities worldwide. Elderlies are the most affected by CVDs, and due to factors such as polypharmacy, multimorbidity, and age-related changes in drugs availability and metabolism, they are highly susceptible to the incidence of drug-drug interactions (DDIs). DDIs are among the many drug-related problems leading to negative outcomes among inpatients and outpatients. Thus, it is important to investigate the incidence, involved drugs, and factors related to DDIs to properly optimize pharmacotherapy regimens for these patients. Aim: To find out the incidence of DDIs, drugs most frequently implicated, and significant predictors associated with these interactions among hospitalized patients in the cardiology unit of Sultan Qaboos University Hospital (SQUH) in Muscat, Oman. Methods: This retrospective cross-sectional study included 215 patients. Micromedex Drug-Reax® was used to identify potential DDIs. Data extracted from patients' medical records was collected and analyzed. Univariable and multivariable linear regression was applied to determine the predictors of the total number of the observed DDIs. Results: A total of 2057 DDIs were identified, with a median of 9 DDIs per patient (IQR = 12-5). Patients with at least one drug-drug interaction accounted for 97.2% of all the included patients. Majority of DDIs were of major severity (52.6%), fair level of documentation (45.5%), and pharmacodynamic basis (64.8%). Interactions between Atorvastatin and Clopidogrel were the most frequently observed (9%). Out of all the detected DDIs, around 79.6% of them included at least one antiplatelet. Having diabetes mellitus as a comorbidity (β = 2.564, p < 0.001) and number of drugs taken during the hospitalization period (β = 0.562, p < 0.001) were factors positively associated with the frequency of DDIs. Conclusion: DDIs were highly prevalent among hospitalized patients in the cardiology unit of SQUH. Patients having diabetes mellitus as a comorbidity and with a high number of administered drugs were at a higher risk of an increased number of DDIs.