BACKGROUND: Untreated pain can have instant and prolonged consequences to behavioral and neurologic outcomes in neonates. Although the use of transversus abdominis plane (TAP) block to minimize postsurgical pain has been demonstrated in neonates, no data regarding the safety of this procedure are available for this patient population. For instance, it is unknown whether plasma levels of local anesthetics are safe in neonates after TAP blocks. The main objective of the current investigation was to evaluate plasma bupivacaine concentrations in neonates having an ultrasound-guided TAP block. METHODS: The study was a prospective, observational study. After general anesthesia was induced, neonates received an ultrasound-guided TAP block with 0.125% bupivacaine and a total volume of 1 mL/kg. Dried blood spot samples were obtained and analyzed for bupivacaine levels at 0, 5, 15, 30, 60, 120 minutes, 4, and 24 hours after the TAP block. RESULTS: Ten neonates were included in the study. The highest 99% upper prediction limit for blood concentration, 0.38 microg/mL, occurred at the 30-minute interval, but it was significantly lower than potentially toxic plasma levels (1.5-2.0 microg/mL). The highest individual concentration was 0.26 microg/mL and occurred at the 30-minute interval. None of the patients demonstrated any potential signs of local anesthetic toxicity. CONCLUSIONS: Our results suggest a low risk of local anesthetic toxicity in neonates after a TAP block. Future studies to determine the efficacy of the TAP block to minimize postsurgical pain in this patient population are warranted.