OBJECTIVES: Recent re-pricing of the ritonovir (RTV) has been criticized as making the antiretroviral drug unaffordable. These criticisms generally considered only cost and not cost-effectiveness. Our study re-evaluates a previous cost-effectiveness analysis of RTV while considering re-pricing. METHODS: A previous cost-effectiveness analysis of HIV salvage regimens suggested that therapy including RTV is cost-effective ($37,889 per responding patient), although slightly less cost-effective than a similar regimen using nelfinavir (NFV) ($31,476) (Becker R, Shakur I, “Cost-effectiveness of salvage therapy with delavirdine in NNRTI-naïve patients failing indinavir,” (abs.) Int. Conf. On AIDS, Barcelona, Spain 2002.). Our present study applied 2003 drug prices for the 2 regimens (RTV + saquinivir [SQV] + adefovir [ADV] and NFV + SQV + ADV) with and without delavirdine (DLV) to determine the total drug cost with each regimen. The cost of RTV reflected recent re-pricing from $8.25 to $34.28 per dose. As with the previous study, results from the ACTG 359 trial were used to calculate the cost-effectiveness of the 3-drug regimens versus the four-drug regimens over a 48-week timeframe. The results were compared to the earlier results and sensitivity analyses were run. RESULTS: At 48 weeks, the 2003 cost-effectiveness of treating with a four-drug combination including RTV was $60,963 per responding patient. This reflects a 60.1% increase from the regimen’s incremental cost effectiveness ratio (ICER) in the earlier study. In contrast, the four-drug combination with NFV had an ICER of $34,310, or a 9.0% increase over the combination’s ratio in the previous study. CONCLUSIONS: The re-pricing of RTV has a significant impact on cost-effectiveness analysis involving the drug. This analysis illustrates that studies once showing RTV to be cost-effective may now show less cost-effective compared to other regimens given current prices. Other prior cost-effectiveness studies that included RTV should be re-analyzed in light of the new pricing.