Objective We aim to compare the cost‐effectiveness of the old cytology programme with the new high‐risk human papillomavirus (hrHPV) screening programme, using performance indicators from the new Dutch hrHPV screening programme. Design Model‐based cost‐effectiveness analysis. Setting The Netherlands. Population Dutch 30‐year‐old unvaccinated females followed up lifelong. Methods We updated the microsimulation screening analysis (MISCAN) model using the most recent epidemiological and screening data from the Netherlands. We simulated both screening programmes, using the screening behaviour and costs observed in each programme. Sensitivity analyses were performed on screening behaviour, utility losses and discount rates. Main outcome measures Cervical cancer incidence and mortality rates, number of screening tests and repeat tests, colposcopy referrals by lesion grade, costs from a societal perspective, quality‐adjusted life years (QALYs) gained and cost‐effectiveness. Results The new Dutch cervical cancer screening programme decreased the cervical cancer mortality by 4% and the incidence by 1% compared with the old programme. Colposcopy referrals of women without cervical intra‐epithelial neoplasia grade 2 or worse, increased by 172%, but 13% more QALYs were still achieved. Total costs were reduced by 21%, mainly due to fewer screening tests. Per QALY gained, the hrHPV programme cost 46% less (€12,225) than the cytology programme (€22,678), and hrHPV‐based screening remained more cost‐effective in all sensitivity analyses. Conclusions The hrHPV‐based screening programme was found to be more effective and cost‐effective than the cytology programme. Alternatives for the current triage strategy should be considered to lower the number of unnecessary referrals. Tweetable abstract First results after implementation confirm that HPV screening is more cost‐effective than cytology screening.