OBJECTIVES: Bichat-Claude Bernard hospital (BCB) is one of the reference centers in HIV care in Paris (France) and has established procedures for post-exposure prophylaxis (PEP). Only patients at high risk of contamination received antiretroviral (ARV) treatment. The aim of this study was to describe the use of PEP (occupational or not), and to estimate the impact of treatment cost. METHODS: We conducted a population-based observational cohort study of patients who presented for PEP in BCB in 2007 and 2008. Data collected included details of HIV exposure, drug regimens and treatment cost. RESULTS: In 2008, 498 patients came in emergencies for a possible HIV exposure (+17% more than 2007). The majority were male (61.4%) and presented after sexual exposure (60.6%). Mean age was 31.4+/-0.4 years. Only in 47.6%, ARVs were prescribed (tri-therapy in all cases) according to guidelines. Median time to receive PEP after hospital admission was 1h07. On average, 19+/-1 days of treatment were dispensed per patient. For 2008, the total acquisition cost of PEP drugs was €13,8580 (1.1% of the total HIV treatment budget, +14.6% compared to 2007) equivalent of €171,785 in a societal point of view. Mean cost per patient was €585+/-38. Without discriminating prescription of PEP, the total cost would have been €291,243. Since French recommendations (march 2008) authorizing TDF+FTC (Truvada®) in first intention as AZT+3TC (Combivir®), associated with lopinavir/r, we observed a change in PEP prescription compared to 2007, which explained at 72.5% the cost's increase observed. CONCLUSIONS: The review of cost-effectiveness suggests that PEP may be cost-effective only in certain population subgroups. In our hospital only targeted patients at high-risk received PEP according to guidelines. The cost difference between TDF+FTC and AZT+3TC highlighted here will enable us to begin a revision of local recommendations.