The purpose of this study was to determine the long-term safety and efficacy of carpal tunnel release (CTR) using ultrasound guidance in a group of patients treated by a single physician. The study group consisted of 76 consecutive CTRs performed on 47 patients between June 2017 and April 2019 for whom 1-year follow-up was available. All procedures were performed by the same operator using a single CTR technique. Outcomes included complications; Boston Carpal Tunnel Questionnaire symptom severity (BCTQ-SSS) and functional status (BCTQ-FSS) scores; Quick Disabilities of the Arm, Shoulder, and Hand (QDASH) scores; and a 5-point global satisfaction score (4 = satisfied, 5 = very satisfied). The 47 patients included 27 females and 20 males (ages 31-91 years). Twenty-five patients (50 hands) had simultaneous bilateral CTRs, 4 patients (8 hands) had staged bilateral CTRs, and 18 patients had unilateral CTRs. No complications occurred. Statistically and clinically significant reductions in BCTQ-SSS, BCTQ-FSS, and QDASH scores occurred by 1 to 2 weeks post-CTR and persisted at 1-year (mean 1-year changes vs. pre-CTR -2.11, -1.70, and -44.99, respectively; P < .001 for all). The mean global satisfaction score at 1-year was 4.63. CTR using ultrasound (US) guidance is a safe and effective procedure that produces statistically and clinically significant improvements within 1 to 2 weeks postprocedure that persist to 1 year. Furthermore, simultaneous bilateral CTRs using US guidance are feasible and may be advantageous for patients who are candidates for bilateral CTR.