Objective <p>To investigate the clinical consequences of the medial versus the posterior internal plate fixation in the treatment of closed humeral shaft fracture.</p> Methods <p>A total of sixty-eight patients diagnosed with closed humeral shaft fracture and treated with internal plate fixation via medial and posterior approach were recruited. All participants collect from The First People’s Hospital of Kashgar (Xinjiang, China) between January 2011 and January 2017 and all participants were follow-up at least for 12 month after surgery. 38 participants treated with internal plate fixation via medial approach were assigned as group A, while 30 participants treated with posterior approach were assigned as group B. The <i>t</i>-test (for normally distributed data) and the <i>χ</i>^<i>2</i>-test (for categorical variates) were performed to compared postoperative fracture union, range of motion of affected shoulder and complications between two groups.</p> Results <p>Fracture union and normal range of motion were achieved 94.7% − 92.1% in all participants, respectively achieved 94.7% in group A while 93.3% in group B (<i>P</i> &gt; 0.05). Postoperative complications was 10.5% in group A and 6.7% in group B (<i>P</i> &gt; 0.05). There was no statistical significance regarding clinical outcomes and postoperative complications between two groups (<i>P</i> &gt; 0.05).</p> Conclusion <p>No significant difference of clinical consequences was found between medial and posterior internal plate fixation in the treatment of closed humeral shaft fracture. Furthermore, internal fixation via medial approach can provide better postoperative cosmetic results with concealed scar formation. Therefore, the medial approach is an effective alternative in the treatment of humeral shaft fractures.</p>