Background: Thromboembolic events remain a major cause of morbidity and mortality among patients with cardiovascular disease (CVD) undergoing surgery. Optimal anticoagulant management is critical to balance the dual risks of thrombosis and bleeding in the perioperative setting.

Objective: This systematic review aimed to evaluate the efficacy and safety of traditional and novel anticoagulant medications in preventing thromboembolic events among surgical CVD patients.

Methods: Following PRISMA 2020 guidelines, a structured search was conducted across PubMed, Scopus, Web of Science, Embase, and Google Scholar for studies published between 2010 and 2024. Twelve peer-reviewed studies met inclusion criteria, encompassing randomized trials, cohort studies, and registries evaluating warfarin, heparin, LMWH, and direct oral anticoagulants (DOACs).

Results: The findings demonstrated that DOACs such as apixaban, rivaroxaban, and dabigatran provide efficacy comparable to VKAs with reduced rates of major bleeding (1.5–2.0%) and fewer gastrointestinal complications. However, bleeding risk remained elevated in cardiac surgery and dual antiplatelet therapy contexts. Studies emphasizing preoperative platelet testing and perioperative management protocols showed reduced bleeding and thromboembolic recurrence.

Conclusions: Evidence supports DOACs as effective and safe alternatives to traditional anticoagulants in surgical CVD patients when managed with individualized perioperative protocols. Further large-scale trials are warranted to refine risk stratification and optimize therapeutic decision-making.