Background: Proximal humeral fractures (PHFs) are common injuries that can lead to significant functional impairment. This retrospective cohort study aimed to evaluate the clinical outcomes and complications associated with the use of the Targon PH+ (Fa. Aesculap, Germany) intramedullary nail for the treatment of PHFs. Methods: A subgroup consisting of 70 patients with a mean follow-up of 4.91 years out of 479 patients who underwent treatment with the Targon PH+ intramedullary nail for PHFs at a single center between 2014 and 2021 were included. Patient-reported outcome measures (PROMs) and health-related quality of life (HRQoL) were assessed using validated German versions of the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, American Shoulder and Elbow Surgeons (ASES) score, Oxford Shoulder Score (OSS), and EuroQol 5-Dimension 5-Level (EQ-5D-5L). Radiographic assessment was performed using pre- and postoperative imaging. Results: Among the 70 patients of the subgroup who completed follow-up, 21.4% experienced complications, including major complications in 15.7% of cases, all of which were revised (revision rate of 15.7%). Anatomical reduction was achieved in 48,5% of cases. The mean DASH, ASES, and OSS scores were 25.4 ± 22.0, 76.2 ± 21.1, and 38.8 ± 10.3, respectively. Significant correlations were observed among the PROMs, indicating their convergent validity. Additionally, a significant correlation of all used PROMs and patient well-being (HRQoL) was observed. Severe complications and revisions were associated with significantly lower ASES scores (−11.1%, p = 0.013). There was a tendency for PROM scores to slightly decline with increasing fracture complexity, although this trend did not reach statistical significance. Our findings indicate that patients over the age of 65 years tend to exhibit lower scores in PROMs and HRQoL measures. Conclusion: The use of the Targon PH+ intramedullary nail for the treatment of PHFs resulted in satisfactory clinical outcomes and acceptable complication and revision rates. The PROMs and HRQoL measures indicated varying levels of disability and symptoms, with major complications, revision surgery, and age negatively impacting shoulder function after midterm follow-up.