© American Academy of Orthopaedic Surgeons. Introduction:Orthopaedic surgeons are wary of patients with neuromuscular (NM) diseases as a result of perceived poor outcomes and lack of data regarding complication risks. We determined the prevalence of patients with NM disease undergoing total joint arthroplasty (TJA) and characterized its relationship with in-hospital complications, prolonged length of stay, and total charges.Methods:Data from the Nationwide Inpatient Sample from 2005 to 2014 was used for this retrospective cohort study to identify 8,028,435 discharges with total joint arthroplasty. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify 91,420 patients who had discharge diagnoses for any of the NM disorders of interest: Parkinson disease, multiple sclerosis, cerebral palsy, cerebrovascular disease resulting in lower extremity paralysis, myotonic dystrophy, myasthenia gravis, myositis (dermatomyositis, polymyositis, and inclusion-body myositis), spinal muscular atrophy type III, poliomyelitis, spinal cord injury, and amyotrophic lateral sclerosis. Logistic regression was used to estimate the association between NM disease and perioperative outcomes, including inpatient adverse events, length of stay, mortality, and hospital charges adjusted for demographic, hospital, and clinical characteristics.Results:NM patients undergoing TJA had increased odds of total surgical complications (odds ratio [OR] = 1.21; 95% confidence interval [CI], 1.17 to 1.25; P < 0.0001), medical complications (OR = 1.41; 95% CI, 1.36 to 1.46; P < 0.0001), and overall complications (OR = 1.32; 95% CI, 1.28 to 1.36; P < 0.0001) compared with non-NM patients. Specifically, NM patients had increased odds of prosthetic complications (OR = 1.09; 95% CI, 0.84 to 1.42; P = 0.003), wound dehiscence (OR = 5.00; 95% CI, 1.57 to 15.94; P = 0.0002), acute postoperative anemia (OR = 1.20; 95% CI, 1.16 to 1.24; P < 0.0001), altered mental status (OR = 2.59; 95% CI, 2.24 to 2.99; P < 0.0001), urinary tract infection (OR = 1.45; 95% CI, 1.34 to 1.56; P < 0.0001), and deep vein thrombosis (OR = 1.27; 95% CI, 1.02 to 1.58; P = 0.021). No difference of in-hospital mortality was observed (P = 0.155).Discussion:Because more patients with NM disease become candidates of TJA, a team of neurologists, anesthesiologists, therapists, and orthopaedic surgeon is required to anticipate, prevent, and manage potential complications identified in this study.Level of Evidence:Level III, retrospective cohort study.