Fuzeon(r) (enfuvirtide; ENF), formerly know as T-20, is the first drug from a novel class of antiretroviral known as the HIV fusion inhibitors which has shown high efficacy rates in HIV-1 / AIDS patients who are resistant to conventional antiretroviral (ARV) agents. OBJECTIVE: To analyse the efficacy of adding ENF to an optimised background regimen (OB) in HIV patients. A Markov model was developed to establish the cost-effectiveness of ENF in terms of incremental cost per life year gained (LYG). The model was designed over a time horizon of 10 years with monthly cycles. The analysis was performed from the perspective of the Spanish NHS. The primary clinical outcome was time until death. Efficacy rates and transition probabilities were obtained from reported clinical and epidemiological trials. Resource use data was retrieved from published literature and from advise from a panel of 6 clinical opinion leaders. Unit costs for Spain in Euros 2003 were obtained from published sources. RESULTS: Adding ENF to OB increases patient's life expectancy by 1,6 years (4.6 years with OB vs. 6.2 years with ENF + OB). Total costs are €116,718 for OB and €155,674 with ENF + OB, mainly due to the fact that increasing life expectancy for a given cohort of patients increases resource use and costs. CONCLUSIONS: Incremental cost per life year gained with ENF is €24,780. ENF used in combination with an OB regimen increases life expectancy for HIV-1 treated patients who are highly ARV-experienced, resulting in an economically efficient treatment option.