OBJECTIVE To determine the public health and economic implications of solvent-detergent-treated frozen plasma (SD FP). While this processing technique nearly eliminates the risk of transmitting lipid-enveloped viruses (hepatitis B and C and human immunodeficiency virus), it has associated costs and, because it requires pooling many plasma units, may increase risks of nonenveloped virus transmission. METHODS A previously published Markov decision analysis model was modified to assess transfusion-related outcomes in hypothetical cohorts of plasma recipients. In-hospital mortality and other characteristics were determined in 61 patients receiving plasma transfusions at a medium-sized tertiary care center to provide data for the model. Other parameters were obtained from the medical literature. METHODS Expected SD FP costs, benefits, and cost-effectiveness, assessed as cost per quality-adjusted life-year saved. RESULTS Compared with untreated plasma, a unit of SD FP produces a net benefit of 35 minutes in quality-adjusted life expectancy at a cost of about $19. Extrapolated to the 2.2 million plasma units transfused annually in the United States, SD FP would save 147 quality-adjusted life-years at a cost of $42.5 million. The marginal cost-effectiveness, $289,300 per quality-adjusted life-year saved in the baseline analysis, was most sensitive to estimates of SD treatment cost and the clinical setting of plasma use. In sensitivity analysis, the net benefit of SD FP was negated by the existence of even a minute risk of nonenveloped virus infection. CONCLUSIONS From a public health perspective, the relatively high costs and small benefits of reducing enveloped virus infection risks with SD FP (and the additional risks of noneveloped virus transmission) do not appear to justify widespread implementation of this new technology.