BACKGROUND: Since 2022, self-sampling has been recommended in Sweden's cervical screening program. Despite still being used primarily for long-term non-attendees, its expected increase in use raises interest in molecular triage methods applicable to self-collected samples. Postmenopausal women face screening challenges due to physiological changes, making this group particularly relevant for evaluating alternative strategies. This study models the cost-effectiveness of different sampling and triage methods in identifying histological high-grade squamous intraepithelial lesions (HSIL) in women aged 60-69 years. METHODS: Using real-world data, this study compares the cost-effectiveness of currently implemented strategy based on professional HPV sampling and combination triage with genotyping and cytology, with modelled strategies based on self-sampling and various molecular triage. The comparison evaluates healthcare resource use and the number of identified histological HSIL cases. The analysis focuses on a single screening cycle, re-testing of invalid samples or screening-positive/triage-negative women are not addressed. RESULTS: Screening with molecular triage either leads to decreases in effect, i.e. fewer histological HSIL identified, or significant cost increases due to higher rate of HPV-positive screening samples and higher number of colposcopy follow-ups. CONCLUSIONS: Molecular triage, whether used with self-sampling or professional sampling, does not appear cost-effective for identifying HSIL in this age group compared to the current screening strategy.