BACKGROUND The three currently used methods of treatment: namely open reduction plate osteosynthesis (ORPO), Minimally invasive plate osteosynthesis (MIPO), antegrade intramedullary nailing(IMN) are all reported as satisfactory procedures for treatment of humeral shaft fractures. However none of the published reports have a comparison of superiority of one procedure over the other. We evaluated the clinical, radiological and functional outcome of the three procedures. METHODS We studied adult patients with humerus shaft fractures over a period of 2 years from May 2014 to May 2016 in a level 1 trauma center. Forty-four were treated with IMN, 34 treated with ORPO, and 34 with MIPO. The null hypothesis tested in this study is that there is no difference between IMN, ORPO, MIPO with respect to union time, surgical time, complication rate, non-union rate and functional outcome. Functional outcome was studied by comparing the UCLA shoulder and MEP scores in the three groups. RESULTS 112 patients were studied consisting of 83 males and 29 females with mean age of 39 years (range 18-70). IMN group showed early union with mean of 12.73 weeks compared to MIPO (14.45 weeks) and ORPO(13.58 weeks), (p<0.05). MIPO had no events of non-union, as compared to ORPO (5 non-unions) and IMN (10 non-unions), (p=0.04). The range of movement at the shoulder with the UCLA score was significantly better with a score of 32.26 in MIPO as compared to 27.54 in IMN and 28.82 in ORPO (p<0.05). The difference in MEPS score in the three groups was not significant (p=0.31). IMN required a mean of 117.95 minutes intraoperatively as compared to 131 and 150.58 mins in MIPO, ORPO respectively. CONCLUSIONS MIPO is overall better with respect to non-union, functional outcome and complications rate. The surgical time depends on the surgeons' skill and learning curve. Thus considering the advantages and risks involved in the various procedure and surgical acumen, each case should be individualized to have a good outcome. We advocate that MIPO can be safely used as an alternative in treating these fractures.