Background and rationale: Stroke is considered the most common cause of adult disability. Intensive rehabilitation protocols outperform nonintensive counterparts. The subacute stroke phase represents a potential window to recovery. Virtual reality (VR) has been shown to provide a more stimulating environment, allowing for increased patient compliance. However, the quality of current literature comparing VR with standard therapies is limited. Our aim is to measure the impact of VR versus standard therapy on the recovery of the upper limb motor function in patients with stroke in the early subacute recovery phase. Method: This is a randomized, controlled trial that will assign 262 patients to tailor-made standard rehabilitation (TMSR) or TMSR plus immersive VR device. The trial will be conducted in an urban rehabilitation clinic in the United States with expertise in the management of poststroke patients. Patients will be 18 to 70 years of age and in the early subacute period (30-90 days post ischemic stroke). The primary outcome will be the change of Fugl-Meyer Assessment—Upper Extremity (FMA-UE) score, measured at baseline and 13 weeks after randomization. The secondary outcome will be the change in the UK Functional Independence Measure and Functional Assessment Measure (UK FIM-FAM) score at the same time points. Discussion: If the use of VR in the rehabilitation of patients with stroke proves to have a significant impact on their motor recovery, it will constitute an extremely important step into decreasing the functional impairment associated with stroke and the related health care expense burden.