Background Severe cases of carpal tunnel syndrome (CTS) are treated with surgical decompression, for which regional nerve blocks are often administered. There is little data about complications associated with these regional techniques for this surgery. The primary objective was to assess the association of ultrasound-guided regional anesthesia nerve blocks in patients undergoing carpal tunnel release with symptom resolution. Methods This single-institution, retrospective study analyzed all patients undergoing open carpal tunnel release from March 2018 to November 2020. Primary exposure was either regional anesthesia (median and ulnar nerve blocks) or non-regional anesthesia (general anesthesia or local infiltration by surgeon). The primary outcome measurement was symptom resolution at postoperative follow-up at 30-60 days. Secondary outcomes were postoperative surgical site infection, time in operating room (minutes), and post-anesthesia care unit (PACU) length of stay (min). The primary outcome was analyzed using multivariable logistic regression. Results A total of 417 patients were included in this study. Of these, 269 (64.5%) subjects received regional anesthesia as their primary anesthetic. When adjusting for confounders, the use of regional anesthesia was not associated with symptoms not improving at postoperative visit (OR 0.52, 95% CI 0.22 - 1.26, P = 0.15), postoperative surgical site infection (OR 1.47, 95% CI 0.44 - 4.85, p = 0.53), or operating room time duration (p = 0.09). However, the use of regional anesthesia was associated with an approximately 15-minute decrease in PACU length of stay (p < 0.001). Conclusions Regional anesthesia is a safe, effective, and time-efficient method for anesthesia in patients undergoing open carpal tunnel release.