We investigated in a randomised clinical trial whether addition of hrHPV testing (high-risk human papillomavirus) to cytological follow-up after treatment for high-grade CIN (cervical intraepithelial neoplasia 2/3) can lead to a better selection of women at risk for residual/recurrent CIN. We included 210 women with high-grade CIN undergoing treatment in outpatient clinics in The Netherlands. Follow-up was based on cytology alone and cytology combined with hrHPV detection. Our primary outcome measurement was improving specificity for residual/recurrent CIN after treatment. Secondary, we compared health-care costs and impact of individual hrHPV type on the risk of residual/recurrent CIN. Follow-up by abnormal cytology alone (6, 12 and 24 months after treatment according to the Dutch protocol) showed a lower specificity for detection of residual/recurrent CIN than follow-up by abnormal cytology and presence of hrHPV (80 vs. 91%, relative risk 0.87 (95% CI 0.77-0.99)). Both methods showed no significant difference in sensitivity ((86 vs. 100%) RR 0.86 (95% CI 0.63-1.16)). Comparing different post hoc modifications in the strategy of combined testing showed similar test characteristics when low-risk women (normal cytology and hrHPV negative at 6 months) omitted the 12 months visit (specificity 91%, p = 1.00 z = 0.00). Prediction of residual/recurrent CIN by typing of hrHPV could not be confirmed. Total health-care costs using cytology and hrHPV testing during follow-up decreased when low-risk women omit the 12 months visit. Follow-up after treatment for high-grade CIN can be improved by combining cytology with hrHPV testing. We advise combined cytology and hrHPV testing at 6, 12 and 24 months after treatment. Low-risk women may omit the 12 months visit, resulting in cost reduction.