ObjectivePatients with multiple chronic health conditions are often managed in a disjointed fashion in primary care, with annual review clinic appointments offered separately for each condition. This study aimed to determine the cost-effectiveness of the 3D intervention, which was developed to improve the system of care.DesignEconomic evaluation conducted alongside a pragmatic cluster-randomised trial.SettingGeneral practices in three centres in England and Scotland.Participants797 adults with three or more chronic conditions were randomised to the 3D intervention, while 749 participants were randomised to receive usual care.InterventionThe 3D approach: comprehensive 6-monthly general practitioner consultations, supported by medication reviews and nurse appointments.Primary and secondary outcome measuresThe primary economic evaluation assessed the cost per quality-adjusted life year (QALY) gained from the perspective of the National Health Service (NHS) and personal social services (PSS). Costs were related to changes in a range of secondary outcomes (QALYs accrued by both participants and carers, and deaths) in a cost–consequences analysis from the perspectives of the NHS/PSS, patients/carers and productivity losses.ResultsVery small increases were found in both QALYs (adjusted mean difference 0.007 (−0.009 to 0.023)) and costs (adjusted mean difference £126 (£−739 to £991)) in the intervention arm compared with usual care after 15 months. The incremental cost-effectiveness ratio was £18 499, with a 50.8% chance of being cost-effective at a willingness-to-pay threshold of £20 000 per QALY (55.8% at £30 000 per QALY).ConclusionsThe small differences in costs and outcomes were consistent with chance, and the uncertainty was substantial; therefore, the evidence for the cost-effectiveness of the 3D approach from the NHS/PSS perspective should be considered equivocal.Trial registration numberISCRTN06180958