Objectives: To preliminarily assess the effectiveness of a highly viscous antibiotic-loaded hydrogel used as a coating for the prevention of superficial and deep Surgical Site Infections (SSIs) after laminectomy and fusion in instrumented vertebral surgery. Methods: We performed a retrospective cohort analysis on 73 consecutive patients who underwent surgery from June 2018 to December 2019 for degenerative spinal disorders (DSD) or traumatic fractures with segmental instability. Patients received the antibiotic-loaded hydrogel over the implants perioperatively and were observed postoperatively for 12 months. Results: Postoperative evaluations showed no adverse events in the study population. None of the patients reported significant pain or functional limitation after surgery. Post-surgically, computed tomography scans confirmed the correct positioning of instruments. At 12 months follow-up, no infection was recorded in the overall population. Conclusion: This retrospective investigation highlights the importance of adopting measures to prevent SSIs in instrumented vertebral surgery. The intraoperative local use of an antibiotic-loaded hydrogel, complementary to systemic antibiotic therapy, appears to minimize the risk of superficial and deep infection.