Perineural injection therapy with 5% dextrose water is progressively becoming a mainstream method for treating carpal tunnel syndrome. However, its long-term outcome is still unknown. Hence, the purpose of this retrospective study was to investigate the long-term outcome after perineural injection therapy using 5% dextrose water.A total of 185 patients diagnosed with carpel tunnel syndrome at least 1 year post-therapy were enrolled. All the patients underwent ultrasound-guided perineural injection therapy using 10 ml of 5% dextrose water at the outpatient department. In a structured telephone interview, the patients were asked about the outcome post-therapy compared with pre-injection. A symptom relief ≥50% indicated effective outcome, and a symptom relief <50% was indicative of a poor outcome.In total, 88.6% patients reported an effective outcome, and 11.4% rated the outcome as poor, after a mean of 2.2 injections with a mean of 1-3 years' post-injection follow-up. The outcome was significantly related with severity level, and the patients that reported a poor outcome had a significantly higher incidence of severe grade compared with those who reported an effective outcome (52.4% vs 31.7%, P = 0.03). Patients with mild, moderate and severe grades, respectively, required an average of 1.7 (0.1), 2.4 (0.2) and 2.6 (0.3) injections to reach an effective outcome (P = 0.006) (severe vs mild, P = 0.008; moderate vs mild, P = 0.062).Perineural injection therapy is a novel approach for treatment of carpal tunnel syndrome with safe and outstanding long-term effects.