The antiretroviral (ARV) service at Edendale Hospital in Pietermaritzburg, KwaZulu-Natal, South Africa has initiated more than 9,000 adults on therapy since 2004; however, virological outcomes among this patient cohort have not been systematically assessed. We conducted a retrospective chart review of patients initiating ARVs in recent years of the antiretroviral roll-out to determine the efficacy of this program. Clinic records were randomly selected for patients who had initiated ARVs between January 2009 and December 2012. Demographic and virological data were collected. Virological failure was defined as failure to achieve a plasma viral load (VL) <25 copies/ml after 6-12 months of ARV initiation or ≥2 consecutive HIV-RNA VLs ≥400 copies/ml following suppression of <25 copies/ml. Records for 228 individuals were reviewed. Twenty-one (9%) individuals experienced virological failure necessitating a regimen change. The median (interquartile range, IQR) duration of antiretroviral exposure was 19 (11-31) months. Individuals experiencing virological failure did not differ from individuals experiencing success with regards to sex, age, baseline hemoglobin, creatinine, alanine aminotransferase level, or weight (p>0.05) except for having a lower baseline CD4 [median 74 (IQR 31-94) versus 142 (IQR 61-211) cells/μl; p=0.0036 (Mann-Whitney U test)]. No differences were observed between groups in type of ARV regimen, WHO stage at time of ARV initiation, or tuberculosis status. Therefore, using a relatively strict definition of virological failure, we observed that virological success was achievable in over 90% of individuals at the Edendale Hospital ARV clinic. Lower baseline CD4 was associated with greater propensity toward virological failure.