To provide the neurological and neurosurgical communities with case evidence of postoperative multiple sclerosis (MS) relapse, literature review to support operative stress-induced relapse and recommendations for perioperative prophylaxis to prevent relapse in patients undergoing surgery. Two case studies are presented with recommendations based on an extensive review of the medical literature and personal experience to support perioperative prophylactic suggestions. Both patients fully recovered to preoperative functional status after treatment. We now routinely implement perioperative prophylaxis to MS patients undergoing surgery at our institution with no complications to date. Perioperative prophylaxis in patients with MS undergoing surgery can prevent relapse. It is of utmost importance that the surgical community realizes that prophylactic treatment is available and should be utilized during elective and emergent surgical situations.

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