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STUDY DESIGN Retrospective, single-center, cohort study. OBJECTIVE Investigate whether the incidence of postoperative delirium in older adults undergoing spinal fusion surgery is associated with postoperative muscle relaxant administration. SUMMARY OF BACKGROUND DATA Baclofen and cyclobenzaprine are muscle relaxants frequently used for pain management following spine surgery. Muscle relaxants are known to cause central nervous system side effects in the outpatient setting and are relatively contraindicated in individuals at high-risk for delirium. However, there are no known studies investigating their side effects in the postoperative setting. METHODS Patients over 65 years of age who underwent elective posterior lumbar fusion for degenerative spine disease were stratified into two treatment groups based on whether postoperative muscle relaxants were administered on postoperative day 1 as part of a multimodal analgesia regimen. Doubly robust inverse probability weighting (IPW) with cox-regression for time-dependent covariates was used to examine the association between postoperative muscle relaxant use and the risk of delirium while controlling for variation in baseline characteristics. RESULTS The incidence of delirium was 17.6% in the 250 patients who received postoperative muscle relaxants compared to 7.9% in the 280 patients who did not receive muscle relaxants (P=0.001). Multivariate analysis to control for variation in baseline characteristics between treatment groups found patients who received muscle relaxants had a 2.00 (95% CI: 1.14-3.49) times higher risk of delirium compared to controls (P=0.015). CONCLUSION Postoperative use of muscle relaxants as part of a multi-modal analgesia regimen was associated with an increased risk of delirium in older adults after lumber fusion surgery. Although muscle relaxants may be beneficial in select patients, they should be used with caution in individuals at high risk for postoperative delirium. Additional work is needed to further examine the risks and benefits of postoperative muscle relaxant administration. LEVEL OF EVIDENCE 3.