Objective To examine the cost-effectiveness of nurse-led stroke aftercare addressing psychosocial outcome at 6 months post stroke, compared with care-As-usual. Design Economic evaluation within a comparative effectiveness research design. Setting Primary care (2016-2017) and community settings (2011-2013) in the Netherlands. Participants Persons who suffered from ischaemic or haemorrhagic stroke, or a transient ischaemic attack and were discharged home after visiting the emergency department, hospitalisation or inpatient rehabilitation. Interventions Nurse-led stroke aftercare at 6 months post stroke addressing psychosocial functioning by providing screening, psycho-education, emotional support and referral to specialist care when needed. Care-As-usual concerned routine follow-up care including secondary prevention programmes and a consultation with the neurologist at 6 weeks post stroke. Primary and secondary outcome measures Main outcome measure of cost-effectiveness was quality-Adjusted life years (QALYs) estimated by the quality of life measured by the five-dimensional, three-level EuroQol. Costs were assessed using a cost-questionnaire. Secondary outcomes were mood (Hospital Anxiety and Depression Scale) and social participation (Utrecht Scale for Evaluation of Rehabilitation-Participation) restrictions subscale. Results Health outcomes were significantly better in stroke aftercare for QALYs ("=0.05; 95% CI 0.01 to 0.09) and social participation ("=4.91; 95% CI 1.89 to 7.93) compared with care-As-usual. Total societal costs were €1208 higher in stroke aftercare than in care-As-usual (95% CI-€3881 to €6057). Healthcare costs were in total €1208 higher in stroke aftercare than in care-As-usual (95% CI-€3881 to €6057). Average costs of stroke aftercare were €91 (SD=€3.20) per person. Base case cost-effectiveness analyses showed an incremental cost-effectiveness ratio of €24 679 per QALY gained. Probability of stroke aftercare being cost-effective was 64% on a €50 000 willingness-To-pay level. Conclusions Nurse-led stroke aftercare addressing psychosocial functioning showed to be a low-cost intervention and is likely to be a cost-effective addition to care-As-usual. It plays an important role by screening and addressing psychosocial problem, not covered by usual care.