Objective To quantify the probabilities of HPV-persistence, viral clearance, or treatment at 24 months in women with CIN2 managed conservatively; describing the determinants of the decision for conservative management, losses to follow-up, and histological findings in treated women. Design Prospective single-arm intervention study. Setting HPV-based pilot screening in Vallecamonica-Sebino, Italy. Population Women with biopsy-confirmed CIN2. Methods Women with CIN2 assessed as low-risk by gynecologists were proposed for conservative management, those who refused received treatment, those who accepted were followed up with HPV, cytology, and colposcopy at 6, 12 and 24 months, then if lesion persisted, treatment was recommended. Competing-risk models were used for investigating the determinants of viral clearance and log-binomial models for the determinants of decision for conservative management and loss to follow up. Main outcome measures Clearance, treatment, or HPV-persistence at 24 months; decision for conservative management and follow-up losses. Results 180 out of 352 women with CIN2 chose conservative management. Within 24 months, 40.6% of women (95% CI 32.8-48.8%) achieved viral clearance, 43.9% (95% CI 35.9-52.1%) underwent delayed treatment, and 15.5% (95% CI 10.2-22.2%) remained HPV-positive. Younger age, immediate colposcopy referral, low-grade cytological and grade I colposcopy were associated with the conservative management decision. Women diagnosed during subsequent screening rounds were more likely to achieve viral clearance (Hazard Ratio 1.95 (95% CI 1.11–3.40)) and had better adherence to follow-up tests. Two cases of invasive carcinoma were identified in treated women. Conclusions Women diagnosed in later HPV screening rounds are more suitable candidates for safe and effective conservative management.