BACKGROUND AND OBJECTIVES: The impact of the patient state at time of placement of regional blocks on the risk of complications is unknown. Current opinion is based almost entirely on case reports, despite considerable interest in the question. Analyzing more than 50,000 pediatric regional anesthesia blocks from an observational prospective database, we determined the rate of adverse events in relation to the patient's state at the time of block placement. Primary outcomes considered were postoperative neurologic symptoms (PONSs) and local anesthetic systemic toxicity (LAST). Secondary outcome was extended hospital stay due to a block complication. METHODS: The Pediatric Regional Anesthesia Network is a multi-institutional research consortium that was created with an emphasis on rigorous, prospective, and complete data collection including a data validation and audit process. For the purpose of the analysis, blocks were divided in major groups by single injection versus continuous and by block location. Rates were determined in aggregate for these groups and classified further based on the patient's state (general anesthesia [GA] without neuromuscular blockade [NMB], GA with NMB, sedated, and awake) at the time of block placement. RESULTS: Postoperative neurological symptoms occurred at a rate of 0.93/1000 (confidence interval [CI], 0.7-1.2) under GA and 6.82/1000 (CI, 4.2-10.5) in sedated and awake patients. The only occurrence of PONSs lasting longer than 6 months (PONSs-L) was a small sensory deficit in a sedated patient (0.019/1000 [CI, 0-0.1] for all, 0.48/1000 [CI, 0.1-2.7] for sedated patients). There were no cases of paralysis. There were 5 cases of LAST or 0.09/1000 (CI, 0.03-0.21). The incidence of LAST in patients under GA (both with and without NMB) was 0.08/1000 (CI, 0.02-0.2) and 0.34/1000 (CI, 0-1.9) in awake/sedated patients. Extended hospital stays were described 18 times (0.33/1000 [CI, 0.2-0.53]). The rate for patients under GA without NMB was 0.29/1000 (CI, 0.13-0.48); GA with NMB, 0.29/1000 (CI, 0.06-0.84); sedated, 1.47/1000 (CI, 0.3-4.3); and awake, 1.15/1000 (CI, 0.02-6.4). CONCLUSIONS: The placement of regional anesthetic blocks in pediatric patients under GA is as safe as placement in sedated and awake children. Our results provide the first prospective evidence for the pediatric anesthesia community that the practice of placing blocks in anesthetized patients should be considered safe and should remain the prevailing standard of care. Prohibitive recommendations based on anecdote and case reports cannot be supported.