Constraint-induced movement therapy (CIMT) is among the most developed training approaches for motor restoration of the upper extremity (UE). Methods: Very Early Constraint-Induced Movement during Stroke Rehabilitation (VECTORS) was a single-blind phase ll trial of CIMT during acute inpatient rehabilitation comparing traditional UE therapy with dose-matched and high-intensity CIMT protocols. Participants were adaptively randomized on rehabilitation admission, and received 2 weeks of study-related treatments. The primary endpoint was the total Action Research Arm Test (ARAT) score on the more affected side at 90 days after stroke onset. A mixed model analysis was performed. Results: A total of 52 participants (mean age 63.9 ± 14 years) were randomized 9.65 ±4.5 days after onset. Mean NIHSS was 5.3 ± 1.8; mean total ARAT score was 22.5 ± 15.6; 77% had ischemic stroke. Groups were equivalent at baseline on all randomization variables. As expected, all groups improved with time on the total ARAT score. There was a significant time x group interaction (F = 3.1, p < 0.01), such that the high intensity CIT group had significantly less improvement at day 90. No significant differences were found between the dose-matched CIMT and control groups at day 90. MRI of a subsample showed no evidence of activity-dependent lesion enlargement. Conclusion: Constraint-induced movement therapy (CIMT) was equally as effective but not superior to an equal dose of traditional therapy during inpatient stroke rehabilitation. Higher intensity CIMT resulted in less motor improvement at 90 days, indicating an inverse dose-response relationship. Motor intervention trials should control for dose, and higher doses of motor training cannot be assumed to be more beneficial, particularly early after stroke.