To compare the success of perceived pulpal anesthesia between groups using nitrous oxide/oxygen (N₂O/O₂) and oxygen (O₂) in children premedicated with ibuprofen with symptomatic irreversible pulpitis permanent teeth. Thirty-three children (mean age 10.4 ± 1.9 years) with 33 symptomatic irreversible pulpitis permanent teeth were included in this preliminary study. All children were premedicated with ibuprofen and randomly assigned to receive either N₂O/O₂ (17 participants) or O₂ (16 participants). Four percent articaine with epinephrine 1:100,000 was administered, and vital pulp therapy was performed. Children used the Wong-Baker FACES Pain Rating Scale (WBFPS) to report their pain at baseline as well as during carious dentin removal, pulpal exposure, and pulpal tissue removal steps. The success was determined when the reported WBFPS score was ≤4. The chi-square test was used to compare the success between both groups. The success of pulpal anesthesia was 71% (12/17) and 19% (3/16) in the N₂O/O₂ and O₂ groups, respectively. The success in the N₂O/O₂ group was 52% higher than that in the O₂ group (confidence interval = 22.9% to 80.7%; significant difference p = .003). From the result of this preliminary study, N₂O/O₂ significantly increased the success of perceived pulpal anesthesia in children premedicated with ibuprofen with symptomatic irreversible pulpitis permanent teeth. However, further study with a larger sample is required to confirm this result.