BACKGROUND: The main advantage of lumbar plexus block over neuraxial anesthesia is unilateral blockade; however, the relatively common occurrence of bilateral spread (up to 27%) makes this advantage unpredictable. The authors hypothesized that high injection pressures during lumbar plexus block carry a higher risk of bilateral or neuraxial anesthesia. METHODS: Eighty patients undergoing knee arthroscopy (age 18-65 yr; American Society of Anesthesiologists physical status I or II) during a standard, nerve stimulator-guided lumbar plexus block using 35 ml mepivacaine, 1.5%, were scheduled to be studied. Patients were randomly assigned to receive either a low-pressure (< 15 psi) or a high-pressure (> 20 psi) injection, as assessed by an inline injection pressure monitor (BSmart; Concert Medical LLC, Norwell, MA). The block success rate and the presence of bilateral sensory and/or motor blockade were assessed. RESULTS: An interim analysis was performed at n = 20 after an unexpectedly high number of patients had neuraxial spread, necessitating early termination of the study. Five of 10 patients (50%) in the high-pressure group had a neuraxial block with a dermatomal sensory level T10 or higher. In contrast, no patient in the low-pressure group (n = 10) had evidence of neuraxial spread. Moreover, 6 patients (60%) in the high-pressure group demonstrated bilateral sensory blockade in the femoral distribution, whereas no patient in the low-pressure group had evidence of a bilateral femoral block. CONCLUSIONS: Injection of local anesthetic with high injection pressure (> 20 psi) during lumbar plexus block commonly results in unwanted bilateral blockade and is associated with high risk of neuraxial blockade.