IMPORTANCE: Superior rectus transposition (SRT) with or without medial rectus recession (MRc) has been introduced as an alternative to MRc alone for treatment of esotropic Duane syndrome; however, the effectiveness of these procedures has not been compared previously. OBJECTIVE: To compare the safety and efficacy of MRc and SRT in treatment of Duane syndrome. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review of all patients with esotropic Duane syndrome who underwent surgical treatment from January 1, 2006, through December 31, 2012, in a multispecialty, hospital-based pediatric ophthalmology/adult strabismus practice at Boston Children's Hospital. Patients in the SRT group underwent SRT with or without MRc; those in the non-SRT group underwent unilateral or bilateral MRc. EXPOSURES: Surgical treatment of esotropic Duane syndrome. MAIN OUTCOMES AND MEASURES: Binocular alignment, ocular ductions, head position, stereopsis, and fundus torsion were recorded before surgery and at the 2-month and final postoperative visits. We also evaluated postoperative drift. RESULTS: The medical record review identified 36 patients who underwent 37 procedures, including 19 in the SRT group (13 SRT + MRc and 6 SRT alone) and 18 in the non-SRT group (11 unilateral MRc and 7 bilateral medial rectus resession). Mean MRc was smaller when performed with SRT (3.3 vs 5.3 mm; P = .004). Although the initial deviation was larger in the SRT group, both groups had a similar improvement in esotropia and head turn. Abduction improved by at least 1 unit in 15 of 19 patients in the SRT group (79%) vs 5 of 18 in the non-SRT group (28%). In 24 patients followed up for more than 6 months, mean esotropia decreased from 8.2 to 6.1 prism diopters (Δ) in the SRT group (n = 12) but increased from 7.2 to 10.9Δ in the non-SRT group (n = 12). CONCLUSIONS AND RELEVANCE: The combination of SRT and MRc was more effective than MRc or bilateral medial rectus resession at improving abduction while allowing for a smaller recession to align the eyes and eliminate a compensatory head posture. Although any surgery on the vertical rectus muscles should in theory increase the risk for vertical or torsional complications, to date this theory has not been borne out in our patients. Patients treated with SRT appear to have a reduced likelihood of long-term undercorrection. We therefore recommend SRT with adjustable MRc for treatment of Duane syndrome in patients with larger amounts of esotropia.