The cost-effectiveness of quality assurance programs is often poorly documented, especially for innovative approaches. The authors analyzed the economic effects of an experimental educational outreach program designed to reduce inappropriate drug prescribing, based on a four-state randomized controlled trial (N = 435 physicians). Primary care physicians randomized into the face-to-face group were offered two individualized educational sessions with clinical pharmacists, lasting an average of 18 minutes each, concerning optimal use of three drug groups that are often used inappropriately. After the program, expenditures for target drugs prescribed by these physicians to Medicaid patients decreased by 13%, compared with controls (P = 0.002); this effect was stable over three quarters. Implementation of this program for 10,000 physicians would lead to projected drug savings (to Medicaid only) of $2,050,000, compared with resource costs of $940,000. Net savings remain high, even after adjustment for use of substitution medications. Although there was a ninefold difference in average preintervention prescribing levels between the highest and lowest thirds of the sample, all groups reduced target drug expenditures at the same rate. Targeting of higher-volume prescribers would thus further raise the observed benefit-to-cost ratio from approximately 1.8 to at least 3.0. Net benefits would also increase further if non-Medicaid savings were added, or if the analysis included quality-of-care considerations. Although print materials alone may be marginally cost-effective, print plus face-to-face approaches offer greater net benefits. The authors conclude that a program of brief, face-to-face "detailing" visits conducted by academic rather than commercial sources can be a highly cost-effective method for improving drug therapy decisions. Such an approach makes possible the enhancement of physicians' clinical expertise without relying on restriction of drug choices.