OBJECTIVE: To examine the determinants of a positive visual inspection after acetic acid (VIA), including the relationship of testing positive for high-risk human papillomavirus (HR-HPV), which is the necessary cause of cervical cancer. DESIGN: A prospective cohort study. SETTING: Three clinical sites in rural China. POPULATION: A total of 7541 women aged 25-65 years. METHODS: All women underwent VIA, DNA testing, by two DNA tests performed on both clinician- and self-collected specimens, and HPV E6 oncoprotein testing. Those positive by any test underwent colposcopy and four-quadrant biopsy evaluation. A random sample of women with negative screening results also underwent colposcopy and, if colposcopic abnormalities were observed, four-quadrant biopsy evaluation was performed. Women diagnosed with cervical intraepithelial neoplasia grade 2 (CIN2), or more severe grades (CIN2 + ), underwent treatment. MAIN OUTCOME MEASURE: Testing positive for VIA. RESULTS: Overall, 7.6% (95% confidence interval, 95% CI, 7.0-8.2%) had a positive VIA. Women who tested positive for HPV were more likely to have a positive VIA than women who tested negative for HPV (15.0%, 95% CI 12.9-17.2% versus 6.3%, 95% CI 5.7-6.9%; P < 0.001). Older women were less likely to have a positive VIA (Ptrend  < 0.001), including women with CIN2 +  (Ptrend  < 0.001). A logistic regression model demonstrated that diagnosis (CIN2 +  versus <CIN2; odds ratio, OR, 32; 95% CI 11-100), testing HPV positive with a higher viral load (highest versus lowest; OR 4.3; 95% CI 2.5-7.4), and age (51 years and older versus <38 years; OR 0.22; 95% CI 0.17-0.30) were independent determinants of having a positive VIA. VIA was more likely to be positive for women with CIN2 + having an abnormal colposcopic impression versus women with CIN2 +  regardless of colposcopic impression (71.4 versus 47.2%). CONCLUSIONS: The age of the population and method of disease ascertainment should be considered in the interpretation of any VIA performance.