Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in heart transplantation. However new diagnostic tools (CMV-PCR) as well as new treatment options (valgancyclovir) have been adopted in clinical practice. The aim of this analysis was to evaluate the incidence of CMV infection and disease in the newest era between 2002 and 2008.We studied 201 heart transplant recipients who received quadruple-immunosuppressive therapy. The study population was categorized into 4 groups according to donor and recipient CMV serology at the time of transplantation (D-/R-, D-/R+, D+/R-, D+/R+) and was monitored by quantitative CMV-PCR blood tests. CMV infection was defined as increase of CMV-PCR results ≥1000cps/ml. CMV disease was defined as CMV infection with clinical symptoms. All patients received CMV Ig and CMV-high risk patients (D+/R-) received prophylaxis with valgancyclovir for three months. The incidence of CMV infection and CMV disease was analyzed among the four groups. During the first year after transplantation, CMV infections and disease developed in 61 (30.3%) and 9 (4.5%) patients respectively. However, CMV disease rate was very low (9 cases, 4.5%). There was no death due to CMV infection. Comparison among the groups showed significantly different incidence of CMV infection (D-/R-: 2.3%, D-/R+: 32.5%, D+/R-: 23.5%, D+/R+:47.5%, p<0.05) and CMV disease (D-/R-: 0%, D-/R+: 2.3%, D+/R-: 11.7%, D+/R+:5%, p<0.05). Average time to CMV infection was longer in the D+/R-: 22.4±14.8 weeks vs. 6.7±12.2 weeks in the other groups. In the D+/R- group, CMV infection occurred after the end of CMV prophylaxis. In all cases of CMV infection, PCR levels decreased after start of therapy. There were no gancyclovir resistant CMV infections. In the era of new CMV diagnostic and therapeutic options, CMV infection is diagnosed earlier and therapy can be started before CMV disease occurs. This approach can reduce morbidity and mortality due to CMV infection.