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Purpose To compare the two main surgical approaches to address proximal humerus fractures (PHFs) stratified for Neer fracture types, to demonstrate which approach gives the best result for each fracture type. Methods A literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in PubMed, Web of Science, and Cochrane databases up to 4 January 2022. Inclusion criteria were studies comparing open reduction and internal fixation (ORIF) with deltopectoral (DP) approach and minimally invasive plate osteosynthesis (MIPO) with deltosplit (DS) approach of PHFs. Patient’s demographic data, fracture type, Constant–Murley Score (CMS), operation time, blood loss, length of hospital stay, complications, fluoroscopy time, and radiological outcomes were extracted. Results were stratified for each type of Neer fracture. Results Eleven studies (798 patients) were included in the meta-analysis. No functional difference was found in the CMS between the two groups for each type of Neer (P = n.s.): for PHFs Neer II, the mean CMS was 72.5 (s.e. 5.9) points in the ORIF group and 79.6 (s.e. 2.5) points in the MIPO group; for Neer III, 77.8 (s.e. 2.0) in the ORIF and 76.4 (se 3.0) in the MIPO; and for Neer IV, 70.6 (s.e. 2.7) in the ORIF and 60.9 (s.e. 6.3) in the MIPO. The operation time in the MIPO group was significantly lower than in the ORIF group for both Neer II (P = 0.0461) and Neer III (P = 0.0037) fractures. Conclusion The MIPO with DS approach demonstrated no significant differences in the results to the ORIF with DP approach for the different Neer fractures in terms of functional results, with a similar outcome, especially for the Neer II and III fracture types. The MIPO technique proved to be as safe and effective as the ORIF approach.