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The risk of severe neurologic injury after neuraxial blockade is extremely rare among the general population. However, patients with preexisting neural compromise may be at increased risk of further neurologic sequelae after neuraxial anesthesia or analgesia.We retrospectively investigated 567 patients with a preexisting peripheral sensorimotor neuropathy or diabetic polyneuropathy who subsequently underwent neuraxial anesthesia or analgesia. Patient demographics, neurologic history, the indication and type of neuraxial blockade, complications, and block outcome were collected for each patient.The majority of patients had chronically stable neurologic signs or symptoms at the time of block placement, with very few reporting progression of their symptoms within the last 6 mo. The type of neuraxial technique included spinal anesthesia in 325 (57%) patients, epidural anesthesia or analgesia in 214 (38%) patients, continuous spinal anesthesia in 24 (4%) patients, and a combined spinal-epidural technique in four (1%) patients. Overall, two (0.4%; 95% CI 0.1%–1.3%) patients experienced new or progressive postoperative neurologic deficits, in the setting of an uneventful neuraxial technique. In these patients, the neuraxial block may have contributed to the injury secondary to direct trauma or local anesthetic neurotoxicity around an already vulnerable nerve. Sixty-five (11.5%) technical complications occurred in 63 patients. The most common complication was unintentional elicitation of a paresthesia (7.6%), followed by traumatic (evidence of blood) needle placement (1.6%) and unplanned dural puncture (0.9%). There were no infectious or hematologic complications.The risk of severe postoperative neurologic dysfunction in patients with peripheral sensorimotor neuropathy or diabetic polyneuropathy undergoing neuraxial anesthesia or analgesia was found to be 0.4% (95% CI 0.1%–1.3%). Clinicians should be aware of this potentially high-risk subgroup of patients when developing and implementing a regional anesthetic care plan.