To determine risk factors, frequency, time patterns, and outcome of ganciclovir-related neutropenia in allogeneic marrow transplant recipients, 278 consecutive patients receiving ganciclovir from engraftment until day 100 were studied. In this cohort, 159 patients (57%) had absolute neutrophil counts (ANC) less than 1,500/microL, 112 (41%) had an ANC less than 1,000/microL, 87 (31%) less than 750/microL, and 56 (21%) less than 500/microL for at least 2 consecutive days. Statistically significant risk factors for neutropenia in a Cox model were low marrow cellularity between day 21 and 28 (relative risk [RR] 2.4, P = .0002), hyperbilirubinemia > or =6 mg/dL during the first 20 days (RR 2.5, P = .0001), and elevation of serum creatinine > or =2 mg/dL after day 21 after transplant (RR 2.1, P = .001). Restriction to factors present at engraftment resulted in a similar model with low marrow cellularity, hyperbilirubinemia > or =6 mg/dL, and elevated serum creatinine as significant risk factors. Patients with no risk factor had an incidence of neutropenia of 21%, an incidence of 31% for one risk factor, and of 57% for two or more risk factors (RR 3.8, P = .001). Neutropenia was a negative predictor of overall (RR 2.0, P = .0001) and event-free survival (RR 2.1, P < .0001), and a predictor of relapse (RR 1.7, P = .03) and nonrelapse mortality (RR 2.1, P = .003). Thus, early liver dysfunction, elevated serum creatinine, and low marrow cellularity are risk factors for ganciclovir-related neutropenia. Neutropenia in ganciclovir recipients after marrow transplantation is an independent risk factor for mortality.