The goal of this study was to identify drug-related problems (DRPs) and the factors involved in the imbalance of new oral anticoagulants (NOACs) and vitamin K antagonists in a Lebanese adult population with cardiovascular diseases. An imbalance in the hemostatic systems between procoagulant and anticoagulant factors in circulating blood produces either hemorrhagic or thrombotic conditions. A prospective cross-sectional study was conducted during 5 months in a teaching hospital. All patients at least 18 years of age taking oral anticoagulants were included in the study. A standardized questionnaire was used, and information was obtained from the patients’ profiles and electronic medical records. DRPs were identified and categorized according to the Pharmaceutical Care Network Europe classification system. A total of 258 patients were included. The overall prevalence of DRPs was 87.2%; the highest prevalence was observed in patients taking acenocoumarol (96.0%), in contrast to 76.7% and 59.0% in patients taking dabigatran and rivaroxaban, respectively. Drug interaction was the most frequent DRP (83.3%), followed by inappropriate monitoring (42.6%) and excessive dose (26.7%). Having renal disease, and taking proton-pump inhibitors or nonsteroidal anti-inflammatory drugs were among the factors affecting the international normalized ratio (INR) range (adjusted odds ratio [ORa] = 2.513, 95% confidence interval [CI] 1.238, 5.101; ORa = 2.487, 95% CI 1.139, 5.430 and ORa = 2.114, 95% CI 1.043, 4.286, respectively), whereas smoking and renal disease significantly affected activated partial thromboplastin time (aPTT) (ORa = 8.325, 95% CI 1.577, 43.965 and ORa = 6.922, 95% CI 1.471, 32.570, respectively). Patients taking NOACs had greater aPTT control and fewer DRPs, with a wide therapeutic index enabling administration of fixed doses.