Many mechatronic devices exist to facilitate hand rehabilitation, however few directly address deficits in muscle activation patterns while also enabling functional task practice. We developed an innovative voice and electromyography-driven actuated (VAEDA) glove, which is sufficiently flexible/portable for incorporation into hand-focused therapy post-stroke. The therapeutic benefits of this device were examined in a longitudinal intervention study. Twenty-two participants with chronic, moderate hand impairment [Chedoke-McMaster Stroke Assessment Stage of Hand (CMSA-H = 4)] enrolled > 8 months post-stroke for 18 1-h training sessions ( 3 × week) employing a novel hand-focused occupational therapy paradigm, either with (VAEDA) or without (No-VAEDA) actuated assistance. Outcome measures included CMSA-H, Wolf Motor Function Test (WMFT), Action Research Arm Test, Fugl-Meyer Upper Extremity Motor Assessment (FMUE), grip and pinch strength and hand kinematics. All outcomes were recorded at baseline and endpoint (immediately after and four weeks post-training). Significant improvement was observed following training for some measures for the VAEDA group (n = 11) but for none of the measures for the No-VAEDA group (n = 11). Specifically, statistically significant gains were observed for CMSA-H (p = 0.038) and WMFT (p = 0.012) as well as maximum digit aperture subset (p = 0.003, n = 7), but not for the FMUE or grip or pinch strengths. In conclusion, therapy effectiveness appeared to be increased by employment of the VAEDA glove, which directly targets deficits in muscle activation patterns.