Antegrade intramedullary nailing in humeral shaft fracture has been abandoned by certain orthopedic surgeons because of rotator cuff injury caused by first- and second-generation intramedullary nails (IMNs). However, only a few studies have specifically addressed the results of antegrade nailing for the treatment of humeral shaft fractures with a straight third-generation IMN; thus, complications need to be re-evaluated. We hypothesized that fixation of displaced humeral shaft fractures with a straight third-generation antegrade IMN with the percutaneous technique avoid shoulder problems (stiffness and pain) incurred by first- and second-generation IMNs. This was a retrospective, single-center, nonrandomized study of 110 patients with a displaced humeral shaft fracture between 2012 and 2019 treated surgically with a long third-generation straight IMN. Mean follow-up was 35.6 months (range, 15-44 months). There were 73 women and 37 men with a mean age of 64.7±19 years. All fractures were closed (37.3% 12A1, 13.6% 12B2, and 13.6% 12B3 AO/OTA classification). Mean Constant score was 82±19, Mayo Elbow Performance Score 96±11 and the mean EQ-5D visual analog scale score was 69.7±21.5. Mean forward elevation 150°±40°, abduction 148°±45°, and external rotation 38°±15°. Symptoms associated with rotator cuff disease were present in 6.4%. Evidence of radiographic fracture healing was detected in all but 1 case. One postoperative nerve injury and 1 adhesive capsulitis were present. Overall, 6.3% underwent second surgeries (4.5% were minor surgeries like hardware removal). Percutaneous antegrade intramedullary nailing of humeral shaft fractures with a straight third-generation nail considerably reduced complications related to shoulder problems and achieved good functional results.