Abstract We investigated reasons for clinical follow-up and treatment discontinuation among HIV-infected individuals receiving antiretroviral therapy (ART) in a public-sector clinic and in a workplace clinic in South Africa. Participants in a larger cohort study who had discontinued clinical care by the seventh month of treatment were traced using previously provided locator information. Those located were administered a semistructured questionnaire regarding reasons for discontinuing clinical follow-up. Participants who had discontinued antiretroviral therapy were invited to participate in further in-depth qualitative interviews. Fifty-one of 144 (35.4%) in the workplace cohort had discontinued clinical follow-up by the seventh month of treatment. The median age of those who discontinued follow-up was 46 years and median educational level was five years. By contrast, only 16.5% (44/267) of the public-sector cohort had discontinued follow-up. Among them the median age was 37.5 years and median education was 11 years. Qualitative interviews were conducted with 17 workplace participants and 10 public-sector participants. The main reasons for attrition in the workplace were uncertainty about own HIV status and above the value of ART, poor patient-provider relationships and workplace discrimination. In the public sector, these were moving away and having no money for clinic transport. In the workplace, efforts to minimize the time between testing and treatment initiation should be balanced with the need to provide adequate baseline counseling taking into account existing concepts about HIV and ART. In the public sector, earlier diagnosis and ART initiation may help to reduce early mortality, while links to government grants may reduce attrition.