Background: Postoperative multiple sclerosis (MS) relapses are a concern among patients and providers. Objective: To determine whether MS relapse risk is higher postoperatively. Methods: Data were extracted from medical records of MS patients undergoing surgery at a tertiary center (2000–2016). Conditional logistic regression estimated within-patient unadjusted and age-adjusted odds of postoperative versus preoperative relapse. Results: Among 281 patients and 609 surgeries, 12 postoperative relapses were identified. The odds of postoperative versus preoperative relapse in unadjusted (odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.18–1.79; p = 0.33) or age-adjusted models (OR = 0.66, 95% CI = 0.20–2.16; p = 0.49) were not increased. Conclusions: Surgery/anesthesia exposure did not increase postoperative relapse risk. These findings require confirmation in larger studies.