Background: Although the consensus is that gender does not influence HIV progression, its relevance may depend on the setting. Aim: To study gender differences in HIV progression to AIDS and death from 1986 to 2001 in a cohort of injecting drug user (IDU) seroconverters in Spain. Methods: Risk of AIDS and death in persons infected for the same length of time were compared through Kaplan-Meier, allowing for late entry, and Cox regression adjusting for gender, age, and calendar period (before 1992, 1992-1995, 1996-1998, 1999-2001) Conclusions: HIV progression was lower in female IDU before and after 1997 and their uptake of antiretroviral therapy was higher than male IDU. The inability to detect a reduction in mortality for women during 1999-2001 is probably attributable to lack of power. Differences in severity of addiction, drug using patterns, and competing causes of death may explain these findings.