OBJECTIVES: We compared the cost-effectiveness of alternative fracture risk assessment strategies for people with intellectual disabilities (ID) aged ≥40 years from a UK National Health Services perspective over a lifetime horizon. DESIGN: Cost-effectiveness analysis using a lifetime decision-analytical model. SETTING: UK primary care, with data from literature and national databases. PARTICIPANTS: People with ID. INTERVENTIONS: Three strategies were assessed: (S1) Risk assessment using the UK QFracture score; (S2) use of IDFracture (a fracture risk prediction tool specifically developed for adults with ID); and (S3) conducting a one-time dual-energy X-ray absorptiometry (DXA) scan in all. S1 and S2 were followed by DXA scan for those at risk. At-risk individuals received treatment according to UK practice (bisphosphonates plus vitamin D and calcium for osteoporosis, and vitamin D and calcium alone for osteopenia). PRIMARY OUTCOME MEASURES: Direct healthcare costs and quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: In the base case, S2 (ICER: -£2568/QALY) was dominant (ie, less costly and more effective) and S3 (ICER: £1678/QALY) was cost-effective relative to S1 for major osteoporotic fracture (MOF). For hip fracture, S2 (ICER: £32 116/QALY) and S3 (ICER: £49 536/QALY) were not cost-effective relative to S1 under the National Institute for Health and Care Excellence-recommended cost-effectiveness thresholds. Findings from the sensitivity analyses were predominantly consistent with the base-case results. Subgroup analyses showed that age-specific and gender-specific strategies could be used. CONCLUSION: For people with ID aged ≥40 years, a proactive approach to risk assessment for MOF is not only clinically beneficial, but also cost-effective.