Background: Cytomegalovirus (CMV) infection is a significant concern during the post-transplant period in heart transplant recipients. Both preemptive and prophylactic approaches are used to prevent CMV infection. This study evaluates the impact of these CMV-targeted strategies on infection rates and graft outcomes, reflecting real-world clinical experience. Methods: The prophylactic strategy was defined as initiating antiviral therapy in all at-risk recipients immediately post-transplantation. The preemptive strategy involved administering antiviral treatment only to patients with detected viremia, identified through regular virological monitoring. Results: CMV infection occurred in 50.0% (30/60) of patients in the preemptive group and 20.8% (5/24) in the prophylactic group, representing a statistically significant reduction with prophylaxis (p=0.014). Graft rejection occurred in 16.7% (10/60) of preemptive patients and 20.8% (5/24) of prophylactic patients, with no significant difference between the groups (p=0.652). Conclusion: Prophylactic CMV prevention in heart transplant recipients significantly lowers the incidence of CMV infection compared to preemptive strategies. However, graft rejection rates did not differ significantly between the two approaches.