Thermal ablation is a simple treatment option for HPV‐associated, pre‐cancerous disease, has a low risk of complications and can be undertaken by non‐specialists. For these reasons, it is one of the recommended treatment modalities for cervical cancer screening programs. As part of a screen‐and‐treat demonstration study, 3060 women living with and without HIV, aged 30–65 years, were recruited at an urban site in South Africa. HPV testing stratified the population into those at highest risk for precancerous disease, identifying 529 (17.3%) women with high HPV viral loads on select HPV genotypes and multi‐channel infections indicating their need for treatment. Among this group, visual assessment criteria further stratified this at‐risk population into those suitable versus unsuitable for ablative therapy. 483 (91.3%) of 529 women met visual criteria defining their suitability for ablative treatment and all were treated with thermoablation. Women were followed at 6‐ and 12‐months where HPV testing and colposcopy with histological sampling were performed. HPV persistence at 12 months despite treatment was 51.8%, and detection of histologically confirmed cervical intraepithelial neoplasia grade 2 or higher occurred in 24.0%. Being HIV‐positive, older age, multi‐channel infection, high HPV viral load, and low CD4 count were associated with these indicators of treatment failure. Cervical cancer screening programs that target treatment to the highest risk women are likely to observe higher indicators of treatment failure than less focused programs. Although thermoablation is an approved treatment modality, our results highlight the urgency of finding more effective but safe and practical treatment options for precancerous disease.