Surgical patients with preexisting neurological diseases create greater challenges to perioperative management, and choice of anesthetic is often complicated. We investigated neuraxial anesthesia use in total knee and hip arthroplasty (TKA/THA) recipients with multiple sclerosis or myasthenia gravis compared to the general population. We retrospectively analyzed patients undergoing a TKA/THA with a diagnosis of multiple sclerosis or myasthenia gravis (Premier Health Database, 2006-2019). The primary outcome was neuraxial anesthesia use in multiple sclerosis or myasthenia gravis patients compared to the general population. Secondary outcomes were length of stay, intensive care unit admission, and mechanical ventilation. We measured the association between the aforementioned subgroups and neuraxial anesthesia use. Subsequently, subgroup-specific associations between neuraxial anesthesia and secondary outcomes were measured. We report odds ratios (ORs) and 95% confidence intervals (CIs). Among 2,184,193 TKA/THAs, 7559 and 3176 had a multiple sclerosis or myasthenia gravis diagnosis, respectively. Compared to the general population, neuraxial anesthesia use was lower in multiple sclerosis patients (OR, 0.61; CI, 0.57-0.65; P < .0001) and no different in myasthenia gravis patients (OR, 1.05; CI, 0.96-1.14; P = .304). Multiple sclerosis patients administered neuraxial anesthesia (compared to those without neuraxial anesthesia) had lower odds of prolonged length of stay (OR, 0.63; CI, 0.53-0.76; P < .0001) mirroring neuraxial anesthesia benefits seen in the general population. Neuraxial anesthesia use was lower in surgical patients with multiple sclerosis compared to the general population but no different in those with myasthenia gravis. Neuraxial use was associated with lower odds of prolonged length of stay.