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Background: The benefit of chemoprophylaxis (CPX) agents in preventing venous thromboembolism must be weighed against potential risks. Current literature regarding the efficacy of CPX after laminectomies with or without fusion is limited, with no clear consensus to inform guidelines. Objective: This study evaluated the association between CPX and surgical complications after lumbar laminectomy with and without fusion. Study Design: Retrospective study of patients at a single large academic institution. Methods: The medical records of patients who underwent lumbar laminectomies with or without lumbar fusion from 2018 to 2020 were reviewed for demographics, surgical characteristics, CPX agents, postoperative complications, epidural hematomas, and wound drainage. Patients receiving CPX (n = 316) were compared with patients not receiving CPX (n = 316) via t test following propensity score matching, and patients on CPX were further stratified by fusion status. Results: The CPX group had higher body mass index and American Society of Anesthesiologists grades. Rates of venous thromboembolism, epidural hematomas, infections, postoperative incision and drainage, transfusions, wound dehiscence, and reoperation were not associated with CPX. Moist dressings were more frequent, and average days of drain duration were longer with CPX. Overall postoperative complication rate and length of stay (LOS) were greater with CPX. The fusion subgroup had a lower Charlson Comorbidity Index, had a lower American Society of Anesthesiologists grade, was younger, had more women, and underwent more minimally invasive laminectomies. While estimated blood loss, operative times, and LOS were significantly greater in the fusion group, there was no difference in rate of intraoperative and postoperative complications. Conclusion: CPX after lumbar laminectomies with or without fusion was not associated with increased rates of epidural hematomas, wound complications, or reoperation. Patients receiving CPX had more postoperative cardiac complications, but it is possible that surgeons were more likely to prescribe CPX for higher-risk patients. They also had higher rates of ileus and moist dressings, greater LOS, and longer length of drain duration. Patients who underwent lumbar laminectomy with fusion on CPX tended to be lower risk yet incurred greater blood loss, operative times, LOS, cardiac complications, and hematomas/ seromas than patients not undergoing fusion. Clinical Relevance: This retrospective study compared surgical complications of lumbar laminectomies in patients who received chemoprophylaxis vs patients who did not. Chemoprophylaxis was not associated with increased rates of epidural hematomas, wound complications, or reoperation, but it was associated with higher rates of postoperative cardiac complications and ileus. Level of Evidence: 3. [ABSTRACT FROM AUTHOR]