BACKGROUND Pupillary diameter (PD) monitoring and Analgesia Nociception Index (ANI) (Metrodoloris, Lille, France), an online wavelet transform-based heart rate variability index, have been used in the assessment of pain. OBJECTIVE The aim of this study was to evaluate the capacity of pupillary reflex dilatation and ANI to provide early assessment of regional anesthesia (RA) success following skin incision in children anesthetised with sevoflurane. METHODS A total of 58 children, eligible for RA, were included after sevoflurane induction. The sevoflurane concentration was adjusted to maintain a MAC of 1.3 in oxygen and nitrous oxide, and a RA was performed. Pupillary diameter and ANI were recorded just prior to skin incision and then every 30 s for a period of 2 min. Regional anesthesia failure was defined by an increase in heart rate ≥ 10% occurring during the first 2 mins following incision. RESULTS Thirty-nine and 19 subjects presented RA success and failure, respectively. In the RA failure group, skin incision induced both changes in PD (P < 0.01) and ANI (P < 0.05) within 1 min of incision. Areas under the receiver-operating curves (95% confidence interval) to identify regional anesthesia failure were 0.747 (0.613-0.881) and 0.671 (0.514-0.827) for the minimal value of ANI and the maximal value of PD recorded during the 2-min period from skin incision, respectively. CONCLUSION Both PD and ANI rapidly change after skin incision in case of RA failure. These indices may provide a useful tool alone, or in combination with heart rate changes in the assessment of RA efficacy in children anesthetised with sevoflurane.