A prospective randomized multi-center trial was initiated comparing PCR-based preemptive and empirical antifungal therapy with AmBisome in patients after allogeneic stem cell transplantation. A total of 408 patients were randomized at the time of transplant to the antifungal treatment strategy. PCR screening was planned twice weekly during stay in hospital and once weekly after discharge until day 100 post-transplantation. Antifungal prophylaxis consisted of up to 200 mg fluconazole/day. Antifungal therapy was initiated in the PCR group in PCR+ patients with signs of infection and patients with 2 consecutive positive PCR results, and in the empirical treatment group (group B) after 120 hours of febrile neutropenia not responding to broad-spectrum antibacterial therapy. Antifungal treatment consisted of AmBisome at 3 mg/kg for 3 days (loading dose) followed by AmBisome at 1 mg/kg in clinically stable patients, AmBisome at 3 mg/kg was continued in clinically unstable patients. Treatment was stopped according to pre-defined study rules. The two arms were well balanced with regard to age, gender, donor type, underlying disease and stage, and conditioning regimens applied. Out of 403 evaluable patients 196 were randomized to group A and 207 to group B. AmBisome therapy was initiated in 109 patients in group A and in 76 patients in group B (P This study prospectively compared PCR-based versus empirical antifungal therapy with AmBisome after allogeneic SCT. A reduction in early mortality and a trend for a lower rate of proven invasive fungal infections was documented until day 30 post-transplantation indicating that close fungal PCR monitoring allows to stratify patients at high risk for the subsequent development of invasive fungal infections. Survival at day 100 and 180 post-transplantation was not different.