Background: Mechanical and bioprosthetic valves are widely used for both aortic and mitral valve replacement, yet long-term survival, complication rates, and reoperation needs differ significantly based on prosthesis type and patient age. The optimal prosthesis choice in South Asian populations remains insufficiently studied, particularly due to differences in anticoagulation adherence, younger surgical demographics, and varying access to postoperative care. Objective: To compare the long-term prognosis of patients receiving mechanical versus bioprosthetic aortic and mitral valve replacements across major cardiac centers in Bangladesh. Methods: A multicenter retrospective cohort study analyzed patients aged ≥18 years who underwent isolated aortic or mitral valve replacement between 2008–2016, with ≥10 years of follow-up. Primary endpoints included long-term survival and freedom from reoperation. Secondary endpoints included thromboembolism, major bleeding, structural valve degeneration (SVD), and endocarditis. Kaplan-Meier survival analysis and Cox proportional hazard models were used to determine adjusted prognostic differences. Results: Among 2,428 patients (mean age 54.2 ± 11.6), 61% received mechanical valves. Mechanical valves showed superior 10-year freedom from reoperation (93.7% vs. 71.4%, p < .001), while bioprosthetic valves demonstrated lower major bleeding rates (4.8% vs. 14.1%, p < .001). Mortality benefits differed by age: patients <60 years had better survival with mechanical valves (HR 0.71; 95% CI 0.52–0.95), while those ≥70 years had better survival with bioprosthetic valves (HR 0.68; 95% CI 0.49–0.94). Conclusion: Mechanical valves offer superior durability and lower reoperation rates, especially in younger patients, while bioprosthetic valves provide better bleeding outcomes and survival benefits in elderly patients. Individualized valve selection based on age, anticoagulation feasibility, and comorbidities is crucial.