Background: The RV144 trial on the ALVAC/AIDSVAX candidate HIV vaccine, carried out in Thailand, showed short-lived protection against infection. Methods: Using a deterministic compartmental model we explored the potential impact of this vaccine on heterosexual HIV transmission in Thailand. Both one-off vaccination strategies, as well as strategies with regular boosting, either annually or every two years, were explored. Both targeting the general adult population and prioritizing sex workers were modeled. The impact of risk compensation among high risk groups, as well as whether higher levels of safe sex in high risk groups could be an alternative to vaccination, was studied. Results: One-off vaccination campaigns had only transient effects, and boosting appears to be a key component of successful vaccination campaigns. Intensive vaccination campaigns may reduce HIV incidence by up to 75% after 10 years of vaccination. Targeting only sex workers has a smaller impact but has a more favorable cost-benefit ratio. Risk compensation has the potential of undoing much of the benefits of a vaccination program and may even increase incidence. In contrast, higher levels of safe sex among sex workers would provide a viable alternative to vaccinating this group. Discussion: The new vaccine holds promise for controlling HIV in Thailand and similar countries. In view of the short lived protection of the vaccine, regular boosting of immunity as well as avoidance of risk compensation are essential. Targeting sex workers would achieve the greatest reduction in incidence per vaccination and may be considered for expensive vaccines but its cost-effectiveness has to be compared to alternatives. (C) 2011 Elsevier Ltd. All rights reserved.