OBJECTIVE: To investigate the effect of gender on mortality of HIV-infected adults receiving antiretroviral therapy (ART) and its possible reasons. METHODS: A retrospective study to review the records for outcomes of adult cases receiving ART at Mzuzu Central Hospital, Malawi, between July 2004 and December 2006. RESULTS: Over the study period, 2838 adult AIDS patients received ART. Of these, 2029 (71.5%) were alive and still on ART, 376 (13.2%) were dead and 433 (15.3%) were lost to follow-up. Survival analysis with Kaplan-Meier estimator showed significantly higher survival rates among females than males in WHO stage 1, 2 and 3 (both P < 0.0001) and borderline in stage 4 (P = 0.076). The Cox model revealed a death hazard ratio (males vs. females) of 1.70 (95% confidence interval 1.35-2.15) after controlling for WHO clinical stages, body mass index and age. More men than women were lost to follow-up in all occupations except health workers. CONCLUSIONS: The most important reasons for a higher mortality in male patients starting ART may relate to their seeking medical care at a more advanced stage of immunodeficiency and poorer compliance with therapy. The issue needs to be addressed in scaling up ART programmes in Africa.