Prism adaptation, the preoperative use of prisms in acquired esotropia to determine the maximum angle of strabismus and to estimate fusional potential, has been suggested as a method of improving the results of initial surgery and minimizing the rate of reoperation. We performed a prospective, randomized, multicenter clinical trial of the effectiveness of prism adaptation. Two levels of randomization were used. Sixty percent of the patients underwent prism adaptation and 40% did not. Of those who responded to prisms with motor stability and sensory fusion, half underwent a conventional amount of surgery and half underwent augmented surgery based on the prism-adapted angle of deviation. Success rates were highest (54 [89%] of 61 patients) in prism adaptation responders who underwent augmented surgery and lowest (92 [72%] of 127 patients) in patients who did not undergo prism adaptation. Prism responders had better results with augmented surgery than with conventional surgery (54 [89%] of 61 patients vs 53 [79%] of 67 patients, P = .23). Our results indicated a significant beneficial overall effect of prism adaptation in patients with acquired esotropia (success rates, 83% vs 72%, P = .04). Although the process requires some additional time and effort, it appears to result in a higher rate of satisfactory alignment.