Little is known about the effect on clinical decision making of nonreimbursement for ineffective medical technologies. Using a time-series design, we studied the effects of cessation of government payment for 12 categories of drugs of questionable efficacy (Drug Efficacy Study Implementation drugs) in a random sample of the New Jersey Medicaid population (N=390 465) and in four cohorts of regular users of these products. We measured changes in the overall levels of prescriptions, expenditures, and physicians' use of substitute drugs. Although withdrawn drugs accounted for 7% of prescriptions in the base year, there was no measurable reduction in overall drug use or expenditures after the regulation; prescription rates actually rose from 0.86 to 1.00 monthly prescriptions per enrollee throughout the 42-month study. Controlling for preexisting trends, an estimated drop in the use of study drugs of 21.7 prescriptions per 1000 enrollees per month was offset by an increase in the use of substitute drugs of 33.7 prescriptions. Both desirable and unimproved therapeutic substitutions were observed. Used alone, curtailment of reimbursement for marginally effective therapies results in both desirable and unintended clinical substitutions and may not reduce costs. Supplementing such restrictions with education may be necessary to promote practices that are more therapeutically and economically appropriate.