OBJECTIVE: With ever-expanding antiretroviral therapy (ART) access among pregnant women in sub-Saharan Africa, it is more than ever important to address the gap in knowledge around ART effectiveness, as measured by HIV viral load, and pregnancy loss. DESIGN: A population-based cohort study. METHODS: The study sample consisted of 3431 pregnancies from 2835 women living with HIV aged 16-35 years old. All women participated in a population-based cohort conducted between 2004 and 2018 in rural KwaZulu-Natal, South Africa. Viral load data were collected at prior surveys and an HIV care registry. The closest available viral load to the date that each pregnancy ended was used and classified as either a pre- or postconception viral load. Logistic regression was used to investigate the association between high viral load (log10 viral load >4.0 copies/ml) and pregnancy loss, defined as either a miscarriage or stillbirth. RESULTS: Pregnancy loss occurred at a rate of 1.3 (95% confidence interval: 1.0-1.8) per 100 pregnancies. There were 1451 pregnancies (42.3%) with postconception viral load measurements. The median time between the viral load measurement and the pregnancy end date was 11.7 (interquartile range: 5.0-25.4) months. We found a higher likelihood of pregnancy loss in women who had high viral loads prior to the outcome of their pregnancy (adjusted odds ratio: 2.38, 95% confidence interval: 1.10-5.18). CONCLUSION: Given the significant relationship between high viral load and pregnancy loss, our study lends further credence to ensuring effective ART through enrolment and retention of pregnant women living with HIV in ART programs, treatment adherence interventions, and viral load monitoring during pregnancy.