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Background Several previous surveys have estimated the rate of major complications that occur after regional anesthesia. However, because of the increase in the use of regional anesthesia in recent years and because of the introduction of new techniques, reappraisal of the incidence and the characteristics of major complications is useful. Methods All French anesthesiologists were invited to participate in this 10-month prospective survey based on (1) voluntary reporting of major complications related to regional anesthesia occurring during the study period using a telephone hotline service available 24 h a day and managed by three experts, and (2) voluntary reporting of the number and type of regional anesthesia procedures performed using pocket booklets. The service was free of charge for participants. Results The participants (n = 487) reported 56 major complications in 158,083 regional anesthesia procedures performed (3.5/10,000). Four deaths were reported. Cardiac arrest occurred after spinal anesthesia (n = 10; 2.7/10,000) and posterior lumbar plexus block (n = 1; 80/10,000). Systemic local anesthetic toxicity consisted of seizures only, without cardiac toxicity. Lidocaine spinal anesthesia was associated with more neurologic complications than bupivacaine spinal anesthesia (14.4/10,000 vs. 2.2/10,000). Most neurologic complications were transient. Among 12 that occurred after peripheral nerve blocks, 9 occurred in patients in whom a nerve stimulator had been used. Conclusion This prospective survey based on a free hotline permanent telephone service allowed us to estimate the incidence of major complications related to regional anesthesia and to provide a detailed analysis of these complications.