Standardized human cytomegalovirus (HCMV) assays were prospectively evaluated to predict HCMV disease. In 135 consecutive adult liver transplantations, pp65-antigenemia, quantitative HCMV-DNA and qualitative pp67-messenger-RNA were determined weekly. No ganciclovir prophylaxis or preemptive treatment was used. One hundred and ten (81.5%) patients showed no HCMV-infection, 25 patients were positive in at least one of the HCMV-tests (18.5%). Four suffered from HCMV viral syndrome (3.0%) and another four from tissue invasive disease. In total, pp65-antigenemia was detected in 18, HCMV-DNA in 22 and pp67-mRNA in 18 patients. The sensitivity and negative predictive value (NPV) for HCMV-disease was 100% for all tests. The PPV for symptomatic HCMV-infection was 47% for pp67 mRNA. In contrast, the PPV of pp65-antigenemia (using a threshold of > 2/200 000 cells) and quantitative PCR (using a cutoff of > 5000 copies/mL) were 80% and 89%, respectively. A cost analysis revealed symptom-triggered or preemptive treatment was less expensive than general ganciclovir prophylaxis, if the incidence of CMV disease was low (<30%). Quantitative human cytomegalovirus (HCMV)-DNA and pp65-antigen assays have a comparable sensitivity and can therefore predict the onset of HCMV symptoms at an early stage. Compared with general prophylaxis, symptom-triggered or preemptive treatment based on one of these assays might reduce the costs and also the danger of ganciclovir resistance.