Objectives/Hypothesis: To determine whether the hypoglossal nerve (XII) can serve as a suitable donor for human laryngeal reinnervation. Study Design: Prospective, nonrandomized. Methods: Measurements were made on patients undergoing open neck procedures to determine the length of XII available and that required to perform XII-recurrent laryngeal nerve (RLN) anastomosis. The morbidity of combined XII and RLN injuries was studied using temporary lidocaine block of the ipsilateral XII in patients with unilateral vocal fold paralysis (UVFP). A pilot series of patients with UVFP who underwent XII-RLN reinnervation was evaluated for morbidity of the procedure, and for improvement in voice and swallowing. Results: In 89 necks the average available length of XII was 2 cm less than that needed to reach the larynx, indicating the RLN stump must be at least 3 cm to allow tension-free anastomosis. Twenty-five patients with untreated UVFP underwent temporary lidocaine block of XII; 8 had slight changes in their speech, none had increased aspiration. Nine patients underwent XII-RLN reinnervation. Postoperative speech analysis correlated well with the findings of the temporary lidocaine block of XII. One-year follow-up of five patients showed excellent voice quality, resolution of any preoperative aspiration, and minimal morbidity. Slight adductory movement of the reinnervated vocal fold was seen during tongue thrust. Electromyography confirmed substantial polyphasic action potentials in the thyroarytenoid muscle. Conclusions: The hypoglossal nerve is a very suitable donor for reinnervation of patients with UVFP. There should be enough length for primary XII-RLN anastomosis in most patients. Donor site morbidity is acceptable. Preoperative lidocaine block of XII is a good predictor of actual donor site morbidity and could be used to assess patients undergoing facial-hypoglossal anastomosis as well.