Background: It is necessary to treat neonatal pain because it may have short and long-term adverse effects. Frenotomy is a painful procedure where sucking, a common strategy to relieve pain, cannot be used because the technique is performed on the tongue. In a previous randomized clinical trial, we demonstrated that inhaled lavender essential oil (LEO) reduced the signs of pain during neonatal frenotomy. We aimed to find out whether inhaled vanilla essential oil (VEO) is more effective in reducing pain during frenotomy than LEO.Methods: Randomized clinical trial with neonates who underwent a frenotomy for type 3 tongue-ties between May and October 2021. Pain was assessed using pre and post-procedure heart rate (HR) and oxygen saturation (SatO2), crying time and NIPS score. Patients were randomized into “experimental” and “control” group. In both groups, we performed swaddling, administered oral sucrose, and let the newborn suck for two minutes. We placed a gauze pad with one drop of LEO (control group) or of VEO (experimental group) under the neonate’s nose for two minutes prior to and during the frenotomy.Results: We enrolled 142 patients (71 per group). Both groups showed similar NIPS scores (2.02 vs 2.38) and crying times (15.3 vs 18.7 s). We observed no differences in HR increase or in SatO2 decrease between both groups. We observed no side effects in either of the groups.Conclusions: We observed no appreciable difference between LEO and VEO, therefore we cannot conclude which of them was more effective in treating pain in neonates who underwent a frenotomy.