Objective To assess triage of HPV-positive women by optical coherence tomography (OCT), with or without HPV16/18 genotyping, compare with cytology. Design A prospective cohort study. Setting The Second Xiangya Hospital in China. Population 813 participants with high-risk HPV(hrHPV)-positive and cervical cytology results received OCT before colposcopy between 1 March 2021 and 1 October 2021. Methods OCT examinations were performed on an outpatient basis. Cytological and histological results during follow-up were obtained from the Department of Pathology at the Second Xiangya Hospital. Main outcome measures OCT and cytology results were compared with the pathological results to calculate sensitivity, specificity, and immediate CIN3+ risk. The advantages and disadvantages of OCT and cytology triage of hr-HPV-positive women were compared. Results HPV16/18 genotyping with OCT triage has a specificity of CIN3+ lesions [61.1%; 95% CI, 57.6%-64.6%], CIN2+ [66.0%; 95% CI, 62.4%-69.6%]. HPV16/18 genotyping with cytology triage has a specificity of CIN3+[44.0%; 95% CI, 40.4%-47.6%], CIN2+ [47.0%; 95% CI, 43.2%-50.8%]. The OCT triage has a higher specificity and positive predictive value(PPV) compared to the cytology with a significant difference. The OCT triage has a similar immediate CIN3+ risk compared to the cytology. Conclusion The combination of OCT and HPV triage (both genotyping and non-genotyping) is feasible in terms of immediate CIN2+/CIN3+ risk, and the OCT triage strategy reduces the number of colposcopies and improves the specificity and positive predictive value of the test compared to the cytological triage strategy.