One hundred and sixty four patients with end-stage osteoarthritis of the hip were randomized to undergo total hip arthroplasty with either a direct lateral approach or a minimally invasive direct anterior approach. The purpose of this study was to compare these two methods in terms of invasiveness, including biomarkers associated with muscle damage and inflammation, and clinical outcomes over the first four postoperative days. Results demonstrated significantly higher serum creatine kinase levels immediately after surgery and at 4 days postoperatively in the direct anterior approach group compared to the direct lateral approach group. In contrast, pain levels over the first four days postoperatively were significantly lower following the direct anterior approach versus the direct lateral approach.