Proximal humeral fractures (PHFs) are fairly common injuries, and their treatment is a challenge. The aim of this study is to compare clinical and functional outcomes of different osteosynthesis techniques. We retrospectively reviewed patients' files and the hospital's digital database between March 2002 and April 2018. We treated surgically 148 patients with 2- and 3-part PHFs: 64 with plate and screws, 53 with intramedullary nailing and 31 with retrograde K-wires. We constituted three groups according to the type of treatment and two subgroups for each according to the number of fragments (Neer II or Neer III). Disabilities of the Arm, Shoulder and Hand (DASH) and Short Form-12 (SF-12) scores were recorded. Mean DASH and SF-12 scores both from the group treated with plate (Group I) and the one subjected to intramedullary nailing (Group II) were statistically superior to results from the patients treated by retrograde K-wires (Group III), while nails showed better functional results than the locking plates. In the first two groups, no difference was found between Neer II and III subgroups, while in Group III the DASH scores were significantly better in Neer II subgroup than those in Neer III subgroup. Avascular necrosis was the most frequent cause of revision surgery in Group I (4 cases) where we had 8 cases of reintervention (12.5%). In Group II, the subacromial impingement was the only cause for revision surgery with 3 cases (5.6%). Intramedullary nails showed better functional results and a lower complication rate than the locking plates. Both techniques showed superior results compared to those available with retrograde K-wires. So the nail seems to be a more reliable and adequate method for treating 2- and 3-part proximal humeral fractures.