Background and purpose We designed an 8-week caregiver-mediated exercise program with e-health support after stroke (CARE4STROKE) in addition to usual care with the aim to improve functional outcome and to facilitate early supported discharge by increasing the intensity of task specific training. Methods An observer-blinded randomized controlled trial in which 66 stroke patient-caregiver couples were included during inpatient rehabilitation. Patients allocated to the CARE4STROKE program trained an additional amount of 150 minutes a week with a caregiver and were compared to a control group that received usual care alone. Primary outcomes: self-reported mobility domain of the Stroke Impact Scale 3.0 (SIS) and length of stay (LOS). Secondary outcomes: motor impairment, strength, walking ability, balance, mobility and (Extended) Activities of Daily Living of patients, caregiver strain of caregivers, and mood, self-efficacy, fatigue and quality of life of both patients and caregivers. Outcomes were assessed at baseline, 8 and 12 weeks after randomization. Results No significant between-group differences were found regarding SIS-mobility after 8 (â 6.21, SD 5.16; P = 0.229) and 12 weeks (â 0.14, SD 2.87; P = 0.961), and LOS (P = 0.818). Significant effects in favor of the intervention group were found for patient's anxiety (â 2.01, SD 0.88; P = 0.023) and caregiver's depression (â 2.33, SD 0.77; P = 0.003) post intervention. Decreased anxiety in patients remained significant at the 12-week follow-up (â 1.01, SD 0.40; P = 0.009). Conclusions This proof-of concept trial did not find significant effects on both primary outcomes mobility and LOS as well as the secondary functional outcomes. Treatment contrast in terms of total exercise time may have been insufficient to achieve these effects. However, caregivermediated exercises showed a favorable impact on secondary outcome measures of mood for both patient and caregiver. Clinical trial registration NTR4300, URL- http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4300.