We aimed to explore the impact of sexual transmission modes on immune reconstitution after combined antiretroviral therapy (cART). We have retrospectively analyzed longitudinal samples from 1557 treated male patients with virological suppression (HIV-1 RNA < 50 copies/ml) for at least 2 years. Both heterosexuals (HET) and men who have sex with men (MSM) patients showed an increasing annual trend in CD4
+
T cell counts after receiving cART (HET, β: 23.51 (cell/µl)/year, 95% CI: 16.70–30.31; MSM, β: 40.21 (cell/µl)/year, 95% CI: 35.82–44.61). However, the CD4
+
T cell recovery rate was much lower in HET patients than MSM patients, determined by both the generalized additive mixed model (
P
< 0.001) and generalized estimating equations (
P
= 0.026). Besides HIV-1 subtypes, baseline CD4
+
T cell counts and age at cART initiation, HET was an independent risk factor for immunological non-responders (adjusted OR: 1.73; 95% CI: 1.28–2.33). HET was also associated with lower probability of achieving conventional immune recovery (adjusted HR: 1.37; 95%CI: 1.22–1.67) and optimal immune recovery (adjusted HR: 1.48, 95%CI: 1.04-2.11). Male HET patients might have poorer immune reconstitution ability even after effective cART. Early initiation of cART after diagnosis and clinical monitoring for male HET patients should be highly emphasized.