BACKGROUND: Pramipexole augmentation of antidepressant treatment for treatment-resistant depression (TRD) has been shown to improve symptom burden over 12 weeks but with some adverse effects compared to placebo augmentation. We aimed to evaluate the cost-effectiveness of pramipexole augmentation for TRD. METHODS: We conducted an economic evaluation as part of the PAX-D trial over 12 and 48 weeks. Two costing perspectives, National Health Service and Personal Social Services (NHS + PSS) and societal, were adopted. The primary outcome was quality-adjusted life year (QALY) based on the EQ-5D-5L. Secondary outcomes included year of full capability (YFC) based on the ICECAP-A, and capability-weighted life year (CWLY) based on the OxCAP-MH. Incremental cost-effectiveness ratios (ICERs), cost-effectiveness planes and cost-effectiveness acceptability curves were reported alongside sensitivity analyses. The trial was registered with ISCTRN (ISRCTN84666271) and EudraCT (2019-001023-13) and is complete. FINDINGS: From the NHS + PSS perspective, mean incremental cost of pramipexole was £60 (95% CI: -£55, £176) over 12 weeks and £811 (95% CI: £110, £1513) over 48 weeks. The difference in QALY gained was 0.012 (95% CI: 0.003, 0.021) over 12 weeks and 0.090 (95% CI: 0.036, 0.144) over 48 weeks, equivalent to 4 (95% CI: 1, 8) and 33 (95% CI: 13, 52) days in perfect health. The ICER was £5069/QALY (95% CI: -£3642, £35,608) over 12 weeks and £9007/QALY (95% CI: £2,219, £27,258) over 48 weeks, representing over 90% probability of cost-effectiveness at £20,000/QALY threshold. From the societal perspective, pramipexole was on average cost saving and more effective over 48 weeks. Alternative analyses provided consistent conclusions. INTERPRETATION: Pramipexole augmentation for TRD has demonstrated both clinical and cost-effectiveness. Further trials, directly comparing pramipexole to other augmentation strategies, will be useful in determining the position of this repurposed medication in the treatment pathway of depression. FUNDING: National Institute for Health and Care Research, Efficacy and Mechanism Evaluation Programme.