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Outcomes of HIV-infected children have improved dramatically over the past decade, but are undermined by patient loss to follow-up (LTFU). We assessed patterns of LTFU among HIV-infected children receiving antiretroviral treatment (ART) at a large inner-city HIV clinic in Johannesburg, South Africa between 2005 and 2014.Demographic and clinical data were extracted from clinic records of children under 12 years. Differences between characteristics of children retained in care and LTFU were assessed using Wilcoxon rank sum tests or Pearson χ2 tests. Cox proportional hazard models then identified characteristics associated with LTFU.Of 135 children, the median age at ART initiation was 21.5 months (IQR: 6.3–47.7) with a median follow-up time of 3.3 years (IQR: 1.4–5.0). The incidence rate of LTFU was 10.8 per 100 person-years (95% CI: 8.2–14.4); cumulatively 36% of children were LTFU. Almost a third (n = 39) of children missed a clinic visit, but then returned to care; 77% of these were eventually LTFU. In total, 18% of children had elevated viral loads after 6 or more months of ART. Older age at ART initiation (18–59 months: aHR 1.6, 95% CI: 3.9–14.2) and ever missing a clinic visit (aHR 7.4 95% CI: 3.9–14.2) were independent predictors of LTFU.High rates of LTFU were observed in this primary care clinic. Risks for LTFU included older age (>18 months old) and missed clinic visits. Identifying children who miss scheduled visits and developing strategies directed at retaining them in care is critical to improving long-term pediatric HIV outcomes.