Background: Minimally invasive plate osteosynthesis (MIPO) technique is one of the many options for the fixation of diaphyseal fractures of the shaft of humerus using the anterior approach. We evaluated the clinical, radiographic, and functional outcome using the MIPO technique to fracture shaft of humerus. Materials and Methods: 64 adult patients with diaphyseal fractures of the humerus treated with MIPO between 2014 February and October 2016 were included in the study. Patients with metabolic bone disease, polytrauma, and Gustilo and Anderson type 3 open fractures with injury severity score >16 were excluded from the study. All cases were treated with closed indirect reduction and locking plate fixation using the MIPO technique. The surgery time, radiation exposure, and time for union was noted. The shoulder and elbow function was assessed using the UCLA shoulder and Mayo elbow performance scores, respectively. Results: Of the 64 patients in the study, 38 were males and 26 were females. The mean age was 39 years (range: 22-70 years). 40 of the 64 (84.3%) had the dominant side fractured. We had 16 cases of C2 type; 10 cases of C1 and 10 cases of A2 type; 8 cases of B2 type; 6 cases each of B3, B1, and A1 type; and 2 cases of A3 type of fracture. The mean surgical time was 94.5 minutes (range: 70-120 minutes) and mean radiation exposure was 160.3 seconds (range: 100-220 seconds). The mean radiological fracture union time was 12.9 weeks (range: 10-20 weeks). Shoulder function was excellent in 54 cases (84.3%) and good in remaining 10 cases (15.6%) on the UCLA score. Elbow function was excellent in 52 cases (81.2%), good in 10 cases (15.6%), and fair in 2 case (3.1%) who had an associated olecranon fracture that was fixed by hook plate in the next sitting.