Background: Adherence to care and treatment are essential for HIV-infected individuals to benefit from antiretroviral therapy (ART). We sought to quantify the effects on treatment outcomes of missing visits soon after initiating ART. Methods: We analyzed data from HIV-infected patients initiating ART at Themba Lethu Clinic, Johannesburg, South Africa, from April 2004 to August 2008. We used log-binomial regression to evaluate the relative risk of missing visits during the first six months of ART on immunological response and virologic suppression. Cox models were used to evaluate the relationship between missed visits and mortality and loss to follow up over 12 months. Results: Of 4476 patients, 65% missed no visits, while 26% missed one visit, 7% missed two and 1.6% missed three or more visits during the first six months on treatment. Patients who missed three or more medical or antiretroviral (ARV) visits had a two-fold increased risk of poor CD4 response by six months, while the risk of failing to achieve virologic suppression by six months increased two- to five-fold among patients who missed two and three or more medical or ARV visits. Adjusted Cox models showed that patients who missed two (HR 2.1; 95% CI: 1.0-4.3) and three or more (HR 4.7; 95% CI: 1.4-16.2) medical visits had an increased risk of death, while those who missed two ARV (HR 3.8; 95% CI: 2.5-5.8) or three or more medical (HR 3.0; 95% CI: 1.1-8.1) visits had an increased risk of loss to follow up. Conclusions: Thirty-five percent of patients missed one or more visits in the first six months on treatment, increasing their risk of poorer outcomes. These patients could be targeted for additional adherence counselling to help improve ART outcomes.