This is the final version of the article. Available from the publisher via the DOI in this record. ; BACKGROUND: The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was the biggest ovarian cancer screening trial to date. A non-significant effect of screening on ovarian cancer was reported, but the authors noted a potential delayed effect of screening, and suggested the need for four years further follow-up. There are no UK-based cost-effectiveness analyses of ovarian cancer screening. Hence we assessed the lifetime outcomes associated with, and the cost-effectiveness of, screening for ovarian cancer in the UK, along with the value of further research. METHODS: We performed a model-based economic evaluation. Effectiveness data were taken from UKCTOCS, which considered strategies of multimodal screening (MMS), ultrasound screening (USS) and no screening. We conducted systematic reviews to identify the remaining model inputs, and performed a rigorous and transparent prospective evaluation of different methods for extrapolating the effect of screening on ovarian cancer mortality. We considered costs to the UK healthcare system and measured effectiveness using quality-adjusted life years (QALYs). We used value of information methods to estimate the value of further research. RESULTS: Over a lifetime, MMS and USS were estimated to be both more expensive and more effective than no screening. USS was dominated by MMS, being both more expensive and less effective. Compared with no screening, MMS cost on average £419 more (95% confidence interval £255 to £578), and generated 0.047 more QALYs (0.002 to 0.088). The incremental cost-effectiveness ratio (ICER) comparing MMS with no screening was £8864 per QALY (£2600 to £51,576). Alternative extrapolation methods increased the ICER, with the highest value being £36,769 (£13,888 to dominated by no screening). Using the UKCTOCS trial horizon, both MMS and USS were dominated by no screening, as they produced fewer QALYs at a greater cost. The value of research into eliminating all uncertainty in long-term effectiveness was estimated to be worth up to £20 million, or approximately £5 million for four years follow-up. CONCLUSIONS: Screening for ovarian cancer with MMS is both more effective and more expensive than not screening. Compared to national willingness to pay thresholds, lifetime cost-effectiveness is promising, but there remains considerable uncertainty regarding extrapolated long-term effectiveness. ; This study presents independent research funded by Public Health England. The views expressed are those of the authors and not necessarily those of Public Health England. The funders of this study had no role in the study design, data collection, data analysis, data interpretation or writing of the report. All authors had access to the raw data. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.