OBJECTIVE: To compare clinical results of treating Neer two- and three-part of proximal humeral fractures between anterolateral acromial approach and deltopectoral approach. METHODS: From January 2009 to December 2012, 49 patients with Neer two- and three-part of proximal humeral fractures were treated with locked plate fixation. In anterolateral acromial approach group, there were 22 patients including 9 males and 13 females with an average of (63.2±7.6) years old, while 27 patients in deltopectoral approach including 12 males and 15 females with an average of (62.9±7.0) years old. Operative time, blood loss during operation, fracture healing time and complications were observed and compared, postoperative Constant-Murley scoring and VAS scoring were applied for evaluate function of shoulder joint and pain at 3 months, 1 and 2 years respectively. RESULTS: All patients were followed up from 24 to 41 months with an average of 34.5 months. Operative time, blood loss, fracture healing time in anterolateral acromial approach group was (68.20±7.04) min, (151.30±20.57) ml, (10.88±4.90) weeks respectively, and better than that of in deltopectoral approach group which was (75.81±13.70) min, (242.10±37.25) ml and (13.60±2.45) weeks. Three months after operation, Constant-Murley scoring and VAS score in anterolateral acromial approach group was 88.32±5.45, 0.41±0.63 and better that of in deltopectoral approach group which was 63.53±8.31, 1.65±1.02. There was no significant differences between two groups in Constant-Murley scoring and VAS score at 1 and 2 years after operation. Each group has one case occurred loss of length humerus head height, and there was 1 case with subacromial impingement, 1 case with bolt loose and 2 cases with delayed union in deltopectoral approach. No axillary nerve injury, humeral head necrosis and breakage of internal fixation occurred both of two groups. CONCLUSION: Both of anterolateral acromial approach and deltopectoral approach are effective in treating Neer two- and three-part of proximal humeral fractures, and can obtain excellent outcomes. Moreover, anterolateral acromial approach has advantage of less trauma, less blood loss, shorter operative time, rapid recovery of shoulder joint function and fracture.