Introduction: Cerebral palsy (CP) is a neurodevelopmental condition with a wide range of presentations that usually lead to muscle imbalance culminating with precocious knee and hip arthrosis, often leading to total hip (THA) and knee arthroplasty (TKA). This study sought to determine the following: (1) the inherent differences of in-hospital characteristics and comorbidities between CP and non-CP patients undergoing total joint arthroplasty (TJA) and (2) do patients with CP have an increased risk of perioperative complications after TJA? Methods: The Nationwide Inpatient Sample database from 2005 to 2014 was queried in this retrospective cohort study to compare patient demographics and comorbidities, hospital characteristics, perioperative complications, and length of stay in patients with CP undergoing TJA compared with their non-CP counterparts. Statistical analyses were performed using the Rao-Scott chi-square test and analysis of variance. All analyses took into account the sampling procedure and weighting. Results: A total of 2,062 and 2,193 patients with CP underwent THA and TKA, respectively, during the study period. Both CP groups were younger (P, 0.0001), were more likely to have Medicaid insurance (P, 0.0001), and had longer lengths of hospital stay (P, 0.0001) compared with their non-CP counterparts. Non-CP patients had significantly higher rates of obesity, coronary artery disease, diabetes, and peripheral vascular disease (P, 0.05). However, patients with CP undergoing THA had a lower Charlson Comorbidity Index (P = 0.0002), whereas those undergoing TKA had similar comorbidity profile as the non-CP group (P = 0.097). Both THA and TKA CP patients had a higher risk of overall postoperative complications (P, 0.05) and surgical complications (P, 0.05), in particular acute postoperative anemia (P, 0.05). Conclusion: Despite being younger with fewer comorbidities, patients with CP are at an increased risk of immediate perioperative complications after TJA compared with the general osteoarthritis population. Given that these patients have satisfactory long-term outcomes after TJA, these procedures can be performed successfully for patients with CP with careful medical management and surgical planning. Level of Evidence: Level III, retrospective cohort study.