The question whether the use of cytomegalovirus (CMV)-seronegative versus white blood cell (WBC)-reduced blood components is equally efficacious in preventing transfusion-acquired CMV infection remains unresolved. A total of 829 recipients of CMV-seronegative components were followed in 11 studies, and a total of 878 recipients of WBC-reduced components were followed in 12 studies. Twelve (1.45%) of 829 recipients of CMV-seronegative components and 24 (2.73%) of 878 recipients of WBC-reduced components developed CMV infection in these studies. Among bone marrow transplant (BMT) recipients, the risk of CMV infection was, respectively, 1.63% (11/674) and 3.01% (21/697). Four of 7 controlled studies of CMV-seronegative components and 1 of 3 controlled studies of WBC-reduced components indicated benefit from these special components compared with CMV-unscreened/non-WBC-reduced components. One of 3 controlled studies indicated benefit from CMV-seronegative components, as compared with WBC-reduced components. Across a subset of studies whose results were integrated in a meta-analysis, CMV-seronegative or WBC-reduced components were virtually equivalent to each other when they were compared with CMV-unscreened/non-WBC-reduced components. CMV-seronegative components were associated with a 93.1% reduction in the risk of CMV infection; WBC-reduced components were associated with a 92.3% reduction in risk (summary odds ratio [OR] = 0.069; 95% confidence interval [CI], 0.037-0.128; P < .05; and summary OR = 0.077; 95% CI, 0.031-0.190; P < .05, respectively). However, across 3 studies that compared CMV-seronegative and WBC-reduced components to each other, CMV-seronegative components were associated with a 58% reduction in risk (summary OR = 0.42; 95% CI, 0.22-0.79; P < .05). Thus, a meta-analysis of the available controlled studies indicates that CMV-seronegative blood components are more efficacious than WBC-reduced blood components in preventing transfusion-acquired CMV infection.