Aim: The aim of this study was to compare the efficacy of the pre-emptive and intraoperative use of intravenous acetaminophen in post-circumcision pain in children. Methods: The records of patients who had undergone circumcision were retrospectively evaluated using our database in the Samsun University, Samsun Training and Research Hospital, Department of Pediatric Surgery, Turkey, from May 2021 to May 2022. Patients were divided into two groups based on administration of pre-emptive (Group 1) and intraoperative (Group 2) acetaminophen. Baseline characteristics, vital signs, outcomes, and Face, Legs, Activity, Cry, and Consolability (FLACC) scale scores were then compared between the groups. Results: Two hundred four patients, 95 (46.6%) in Group 1 and 109 (53.4%) in Group 2, were enrolled in the study. No significant difference was determined in terms of mean body mass index, age, length of stay in the recovery room, operative time, or length of hospital stay. Vital findings exhibited no difference in preoperative, induction, intraoperative, or postoperative recordings. Significant differences were observed between the groups’ mean pain scores 30 minutes after surgery (p = 0.024). However, no such significant differences were observed at one and three hours after surgery (p = 0.063 and p = 0.708, respectively). Rescue analgesia was performed in 13 (13.7%) cases in Group 1 and 17 (15.6%) in Group 2 (p = 0.7). Conclusions: Pre-emptive intravenous acetaminophen reduced pain 30 minutes after circumcision. Pre-emptive and intraoperative use of acetaminophen resulted in similar and acceptable efficacy in pain relief one and three hours after surgery.