A static deterministic model was used to estimate the effect of the shift to a triple combination therapeutic standard on the annual AIDS Drug Assistance Program (ADAP) budget, total medical care expenditures, and population health outcomes for New York (NY) state ADAP enrollees. The model used opportunistic disease incidence data from the Multicenter AIDS Cohort Study (MACS) and other studies. Costs of treating opportunistic infections (OIs) and other HIV complications with each type of therapy were derived from treatment algorithms and standard unit costs. CD4+ cell counts were used as an index of need for OI prophylaxis and for determining OI incidence. Treatment with zidovudine-based combination therapy has been shown to increase CD4+ cell counts and reduce OI incidence. The model estimated that a change from monotherapy to triple therapy would have increased NY ADAP budget expenditures per enrollee by 115%. However, total medical system costs per ADAP enrollee (including ADAP costs) would decrease by 0.4% in the base case as a result of reduction in OIs and other HIV sequelae and associated costs. Results are sensitive to the assumed percentage of people taking combination therapy as well as to the assumptions made about the impact of the combination therapy on CD4+ cell count. Total ADAP budget impacts will depend on the growth in ADAP enrollment as a result of the availability of more effective therapies. In conclusion, this model demonstrates how access to newer, more effective HIV drug treatments can reduce the costs of treating OIs and provide major health benefits for ADAP enrollees.