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Glenoid component malposition for anatomic shoulder replacement may result in complications. The purpose of this study was to define the efficacy of a new surgical method to place the glenoid component.Thirty-one patients were randomized for glenoid component placement with use of either novel three-dimensional computed tomographic scan planning software combined with patient-specific instrumentation (the glenoid positioning system group), or conventional computed tomographic scan, preoperative planning, and surgical technique, utilizing instruments provided by the implant manufacturer (the standard surgical group). The desired position of the component was determined preoperatively. Postoperatively, a computed tomographic scan was used to define and compare the actual implant location with the preoperative plan.In the standard surgical group, the average preoperative glenoid retroversion was −11.3° (range, −39° to 17°). In the glenoid positioning system group, the average glenoid retroversion was −14.8° (range, −27° to 7°). When the standard surgical group was compared with the glenoid positioning system group, patient-specific instrumentation technology significantly decreased (p < 0.05) the average deviation of implant position for inclination and medial-lateral offset. Overall, the average deviation in version was 6.9° in the standard surgical group and 4.3° in the glenoid positioning system group. The average deviation in inclination was 11.6° in the standard surgical group and 2.9° in the glenoid positioning system group. The greatest benefit of patient-specific instrumentation was observed in patients with retroversion in excess of 16°; the average deviation was 10° in the standard surgical group and 1.2° in the glenoid positioning system group (p < 0.001). Preoperative planning and patient-specific instrumentation use resulted in a significant improvement in the selection and use of the optimal type of implant and a significant reduction in the frequency of malpositioned glenoid implants.Novel three-dimensional preoperative planning, coupled with patient and implant-specific instrumentation, allows the surgeon to better define the preoperative pathology, select the optimal implant design and location, and then accurately execute the plan at the time of surgery.Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.