Background. OnabotulinumtoxinA injections improve upper-limb spasticity after stroke, but their effect on arm function remains uncertain. Objective. To determine whether a single treatment with onabotulinumtoxinA injections combined with upper-limb physiotherapy improves grasp release compared with physiotherapy alone after stroke. Methods. A total of 28 patients, at least 1 month poststroke, were randomized to receive either onabotulinumtoxinA or placebo injections to the affected upper limb followed by standardized upper-limb physiotherapy (10 sessions over 4 weeks). The primary outcome was time to release grasp during a functionally relevant standardized task. Secondary outcomes included measures of wrist and finger spasticity and strength using a customized servomotor, clinical assessments of stiffness (modified Ashworth Scale), arm function (Action Research Arm Test [ARAT], Nine Hole Peg Test), arm use (Arm Measure of Activity), Goal Attainment Scale, and quality of life (EQ5D). Results. There was no significant difference between treatment groups in grasp release time 5 weeks post injection (placebo median = 3.0 s, treatment median = 2.0 s; t(24) = 1.20; P = .24; treatment effect = −0.44, 95% CI = −1.19 to 0.31). None of the secondary measures passed significance after correcting for multiple comparisons. Both groups achieved their treatment goals (placebo = 65%; treatment = 71%), and made improvements on the ARAT (placebo +3, treatment +5) and in active wrist extension (placebo +9°, treatment +11°). Conclusions. In this group of stroke patients with mild to moderate spastic hemiparesis, a single treatment with onabotulinumtoxinA did not augment the improvements seen in grasp release time after a standardized upper-limb physiotherapy program