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Background: Optimal treatment of proximal humeral fractures (PHF) is still controversial. Therefore, we aim to investigate the influence of fracture reduction after intramedullary nailing of a PHF on the clinical outcome. Methods: Patients treated with intramedullary nail for PHF from 2013–2018, (minimum follow-up 12 months) were retrospectively included. Constant Score (CS), DASH and Simple Shoulder Test (SST) were collected. Postoperative radiographs were used to determine head-shaft-alignment (HSA), head-shaft-displacement (HSD), integrity of the medial hinge and the cranialization of the greater tuberosity (CGT). The results of fracture reduction were categorized as either “anatomical”, “acceptable” or as “malreduction”. Malreduction exists when at least one of the following parameters are present: HSA > 150/< 110°, HSD >5 mm, CTM > 5 mm or lack of integrity of the medial hinge. Results: 42 patients (mean age 65.5 ± 14.1 years, 15 male, 27 female) with a mean follow-up time of 43 months were included. The average CS was 60 ± 30, DASH 49.8 ± 24.3 and SST 62.9 ± 26.9. There was an “anatomic” reduction in 9 (21.4%), “acceptable” in 7 (16.6%) and a “malreduction” in 26 (62%) patients. Comparing the combined “anatomical” and “acceptable” reduction group with the “malreduction” group, worse scores were observed in the “malreduction” group (CS 67.2 vs. 55.2, DASH 45.2 vs. 51.9, SST: 69.3 vs. 58.6) without statistical significance (CS: p = 0.095, DASH: p = 0.307, SST: p = 0.400). By means of multiple logistic regression analyses no statistically significant risk factors were identified for lower DASH, CS and SST scores. Conclusions: Anatomical fracture reduction using intramedullary nails has a positive effect on postoperative outcome for the 3 scores recorded, without reaching statistical significance.