Purpose There is still an ongoing discussion whether a prophylactic or a preemptive therapy against cytomegalovirus (CMV) is superior to reduce the incidence of CMV viremia, acute rejections (AR) or cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). Thus, we evaluated different CMV treatment strategies in this setting. Methods HTx patients (n=56) were retrospectively studied regarding the end points of CMV-free survival viremia, AR, and CAV. The average follow-up was 4.15 years (355 days up to 7.5 years). Patients were classified into 3 groups according to their CMV therapy: preemptive therapy (PRE, n=19), prophylactic drug monotherapy (PROM, either valganciclovir for 3 months or early single dose of 1mg/kg/BW of CMV immunoglobulin, CMVIG, 2 weeks post-HTx, n=18) or prophylactic double drug therapy (PROD, valganciclovir for 3 months plus early single dose of CMVIG, n=19). For statistical analysis X2, X2-log-rank and T-Tests were used. Results Median patient survival was similar: PRE-group 2243 days, PROM-group 2417 days, and PROD-group 2410 days, respectively. However, the median CMV-viremia free survival was different among the groups: 1817 days in the PROD-group, 1459 days in the PROM-group and 1482 in the PRE-group (p=0.52). A subanalysis of patients with high risk for CMV infection (donor+/ recipient-CMV status) the CMV-free survival was significantly higher when patients received double prophylaxis therapy compared to the other two groups (p<0.01). Whether the incidence of AR nor of CAV was not significantly influenced by the choice of CMV treatment regimen. Antiviral medication was discontinuated in 10.5% PRE-group, 38.9% PROM-group, and 31.6% PROD-group, respectively. Conclusion Our study results suggest that early therapy with CMVIG as adjunct to antiviral treatment could prolong CMV-free survival in patients with CMV risk of infection. If a repetitive CMVIG dosing post-HTx will further reduce CMV infection needs to be explored in the future. There is still an ongoing discussion whether a prophylactic or a preemptive therapy against cytomegalovirus (CMV) is superior to reduce the incidence of CMV viremia, acute rejections (AR) or cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). Thus, we evaluated different CMV treatment strategies in this setting. HTx patients (n=56) were retrospectively studied regarding the end points of CMV-free survival viremia, AR, and CAV. The average follow-up was 4.15 years (355 days up to 7.5 years). Patients were classified into 3 groups according to their CMV therapy: preemptive therapy (PRE, n=19), prophylactic drug monotherapy (PROM, either valganciclovir for 3 months or early single dose of 1mg/kg/BW of CMV immunoglobulin, CMVIG, 2 weeks post-HTx, n=18) or prophylactic double drug therapy (PROD, valganciclovir for 3 months plus early single dose of CMVIG, n=19). For statistical analysis X2, X2-log-rank and T-Tests were used. Median patient survival was similar: PRE-group 2243 days, PROM-group 2417 days, and PROD-group 2410 days, respectively. However, the median CMV-viremia free survival was different among the groups: 1817 days in the PROD-group, 1459 days in the PROM-group and 1482 in the PRE-group (p=0.52). A subanalysis of patients with high risk for CMV infection (donor+/ recipient-CMV status) the CMV-free survival was significantly higher when patients received double prophylaxis therapy compared to the other two groups (p<0.01). Whether the incidence of AR nor of CAV was not significantly influenced by the choice of CMV treatment regimen. Antiviral medication was discontinuated in 10.5% PRE-group, 38.9% PROM-group, and 31.6% PROD-group, respectively. Our study results suggest that early therapy with CMVIG as adjunct to antiviral treatment could prolong CMV-free survival in patients with CMV risk of infection. If a repetitive CMVIG dosing post-HTx will further reduce CMV infection needs to be explored in the future.