Background: We analysed the influence of gender on use and outcomes of first-line HAART in a UK cohort. Methods: Analyses included heterosexuals starting HAART from 1998-2007 with pre-treatment CD4 + T-cell count <350 cells/mm 3 and viral load (VL)>500 copies/ml. Virological suppression (<50 copies/ml), virological rebound (>500 copies/ml), CD4 + T-cell counts at 6 and 12 months, clinical events and treatment discontinuation/switch in the first year of HAART were compared using linear, logistic and Cox regression. Results: Compared with women (n=2,179), men (n=1,487) were older and had lower CD4 + T-cell count and higher VL at start of HAART. Median follow-up was 3.8 years (IQR 2.0-6.2). At 6 and 12 months, 72.7% and 75.3% had VL≤50 copies/ml, with no large differences between genders at either time after adjustment for confounders (6 months, OR 0.92 [95% CI 0.76-1.13]; 12 months, OR 1.06 [95% CI 0.85-1.31]). Overall, 79.4% patients achieved virological suppression and 19.2% experienced virological rebound, without gender differences, although men had an increased risk of rebound after excluding pregnant women (adjusted relative hazard [RH] 1.33 [95% CI 1.04-1.71]). Mean CD4 + T-cell count increases at 6 and 12 months were, respectively, 112 and 156 cells/mm 3 overall, with mean differences between men and women of -14.6 cells/mm 3 (95% CI -24.6 - 4.5) and -12.1 cells/mm 3 (95% CI -24.4-0.2) at 6 and 12 months, respectively. Clinical progression was similar in men and women, but men were less likely to experience treatment discontinuation/switch (adjusted RH 0.72 [95% CI 0.63-0.83]). Conclusions: Despite higher discontinuation rates among women, men had an increased risk of virological rebound and slightly poorer CD4 + T-cell count responses. Identifying the reasons underlying treatment discontinuation/ switch may help optimize treatment strategies for both genders.