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<b>Background/Objectives</b>: Hospital-acquired and fracture-related infections remain major complications in orthopedic trauma surgery, with significant clinical and socio-economic impact. Antibacterial implant surface coatings represent a promising strategy to reduce early postoperative bacterial adhesion and biofilm formation. <b>Methods</b>: This retrospective matched case-control study evaluated the clinical effectiveness of an antibiotic-free fast-resorbable hyaluronic acid and poly-d, l-lactide hydrogel (DAC<sup>®</sup>) applied intraoperatively to orthopedic implants. A total of 222 patients with comorbidities who underwent open reduction and internal fixation between May 2023 and April 2024 in two trauma centers were included: 99 patients received the DAC<sup>®</sup> coating and 123 served as controls with standard fixation. The primary endpoint was infection incidence within 6 months; secondary endpoints included wound complications, revision surgery, prolonged antibiotic therapy, and bone healing. <b>Results</b>: Postoperative infection incidence was significantly lower in the DAC<sup>®</sup> group compared with controls (0.7% vs. 5.3%; <i>p</i> = 0.0363). Wound complications were also reduced (1.3% vs. 8.0%; <i>p</i> = 0.028), and only one patient in the DAC<sup>®</sup> cohort required additional surgical interventions or prolonged antibiotic therapy. Bone healing outcomes were comparable between groups, with no delayed unions reported in the treated cohort. <b>Conclusions</b>: Even if larger prospective studies with longer follow-up are required to further confirm these findings and better define long-term safety and effectiveness, the routine intraoperative use of DAC<sup>®</sup> hydrogel without antibiotic loading appears to be a safe and promising strategy to reduce early postoperative infections and wound complications in orthopedic trauma patients with comorbidities.