BACKGROUND: There have been concerns about reduced adherence and HIV virological suppression (VS) amongst clinically well people living with HIV initiating antiretroviral treatment (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HPTN 071 (PopART) trial in South Africa prior to routine national and international implementation. METHODS: This prospective cohort study included adults initiating ART at facilities providing ART irrespective of CD4 count since January 2014. VS (<400 copies/ml), confirmed virological failure (VF) (two consecutive viral loads>1000 copies/ml) and viral rebound were compared between participants in strata of baseline CD4 count. RESULTS: The sample included 1901 participants. VS was 94% or greater amongst participants with baseline CD4 count >/=500 cells/microL at all six-monthly intervals to 30 months of ART. The risk of an elevated viral load (>/=400 copies/ml) was independently lower amongst participants with baseline CD4 count >/=500 cells/microL (3.3%) compared to those with CD4 count 200-499 cell/microL (9.2%) between months 18-30, adjusted relative risk=0.30 (95% CI: 0.12-0.74, P=0.010). The incidence rate of VF was 7.0, 2.0 and 0.5 per 100 person-years amongst participants with baseline CD4 count <200, 200-499 and >/=500 cells/microL, respectively (P<0.0001). VF was independently lower amongst participants with baseline CD4 count >/=500 cells/microL, adjusted hazard ratio (aHR)=0.23, P=0.045; and three-fold higher amongst those with baseline CD4 count <200 cells/microL, aHR=3.49, P<0.0001. CONCLUSION: Despite previous concerns, participants initiating ART with CD4 counts >/=500 cells/microL had very good virological outcomes, being better than those with CD4 counts 200-499 cells/microL.