BACKGROUND: Guyon's canal syndrome is nerve compressive pathology which can lead to sensory and/or motor function deficits. This problem is usually difficult to distinguish from cubital tunnel syndrome and relatively less common than cubital tunnel syndrome. This study evaluated the functional results and patient-reported outcomes following decompression of the ulnar nerve in Guyon's canal. METHODS: Patients who were diagnosed with Guyon's canal syndrome confirmed by electrodiagnostic studies and underwent nerve decompression surgery were included in this study. The functional improvement by examining the Froment's sign, Wartenberg's sign, static two-point discrimination, and Semmes Weinstein monofilament examination as physical examination scores was evaluated. The visual analogue scale of satisfaction and the disabilities of the arm, shoulder, and hand questionnaire were used for the postoperative patient-reported outcome evaluation. RESULTS: From 2003 to 2019, 38 cases had been enrolled with a mean age of 53 years, ranging from 19 to 85 years. There were seven patients with comorbidity of diabetes mellitus and 28 patients who received additional neurolysis combined with the Guyon's release procedure. There were 19 patients with a good response to surgery and 10 patients with a poor surgical outcome due to persistent paresthesia or weakness. After statistical analysis, it was revealed that several influential factors could have been related to a compromised functional outcome, including a symptom duration of more than 3 months, combination with additional neurolysis of ipsilateral extremity, and/or comorbidity with diabetes mellitus. CONCLUSION: It was concluded that promising functional outcomes after surgical release of ulnar neuropathy in Guyon's canal could be achieved if the patients did not need additional neurolysis or the symptom duration was within 3 months.