Background <p>Peripheral nerve surgery is a potential treatment for chronic spastic hemiplegia, but the role of contralateral C7 nerve transfer combined with human acellular nerve allograft remains to be explored. This study aimed to investigate the functional outcomes of contralateral C7 nerve transfer combined with human acellular nerve allograft for spastic upper limb paralysis.</p> Methods <p>From January 2020 to December 2023, 53 patients with unilateral spastic upper limb paralysis completed a 12-month follow-up. 17 patients underwent contralateral C7 nerve transfer combined with human acellular nerve allografts, while 36 received rehabilitation alone. The primary outcome was the change in the Fugl-Meyer Assessment. Safety outcomes included adverse events and changes in muscle strength and motor–sensory function assessment of the arm and hand on the side of the donor C7 nerve.</p> Results <p>The overall Fugl-Meyer Assessment increased by 15.88 ± 3.54 in the surgery group and 2.36 ± 2.34 in the rehabilitation group (difference, 13.52, P &lt; 0.001). Spasticity improvements were observed on the Modified Ashworth Scale for various muscle groups (P &lt; 0.001). Adverse events related to the donor nerve included mild numbness in the radial three digits, slightly weakened triceps brachii strength, and tolerable peripheral neuropathic pain. No other adverse event relative to the bilateral brachial nerve occurred except for the C7 nerve section, and all events resolved within 3&#xa0;months for all patients.</p> Conclusion <p>Our study suggests that the combination of the contralateral C7 nerve transfer and the human acellular nerve allograft may be a viable treatment option for individuals experiencing long-term spastic upper limb impairment following chronic cerebral hemisphere injury.</p> <p><i>Trial registration</i>: This clinical study was registered with the Chinese Clinical Trial Registry, and the registration number is ChiCTR2500099694</p>