Background: Children with abdominal pain in the emergency department (ED) are at particular risk of suboptimal analgesia due to fears of missing appendicitis and absent guidelines. Many still experience pain at discharge. Acetaminophen is the most commonly used analgesic and efficacy of hyoscine butylbromide (HBB) is supported by adult evidence. However, no evidence exists for either agent in children with abdominal pain. Objective: To determine if HBB is superior to acetaminophen for abdominal pain in children. Methods: We will consecutively recruit children 8-17 years presenting to the ED with presumed non-surgical abdominal pain rated >4/10 on the Faces Pain Scale – Revised (FPS-R) and described as colicky, excluding:-Suspected appendicitis or bowel obstruction-Anticholinergic, analgesic, or antispasmodic <12 hours-Peritoneal inflammation-Unable to swallow pills-Hypersensitivity to either intervention-Medically unstable-Previous bowel obstruction, abdominal surgery, myasthenia gravis, liver disease, glaucoma, or recent abdominal trauma (<48 hours)-Toxin ingestion (<24 hours)-Vomiting-Pregnancy Randomization and allocation concealment will be pharmacy-controlled and performed using a computerized random number generator and sequentially numbered, opaque, sealed envelopes, respectively. The physician, research assistant, nurse, and participant will be blinded. Due to perceptible differences, participants will be randomized in a double-dummy approach to:-HBB 10 mg tablet + acetaminophen placebo OR-Acetaminophen 15 mg/kg liquid (maximum 975 mg) + HBB placebo. The primary outcome will be the difference from baseline on the FPS-R at 120 minutes, reflecting HBB’s time to peak plasma concentration. The FPS-R has been validated in children >five years. Secondary outcomes include:-Pain scores at 15, 30, 45, 60, 80, 100, and 120 minutes post-intervention (FPS-R and 100 mm visual analog scale)-Discharge pain score-Rescue analgesia-Time to achieve a 20% reduction in pain-Adverse effects-Recidivism <48 hours-Missed surgical diagnoses (National Ambulatory Care Reporting System (NACRS) database)-Caregiver satisfaction (five-item Likert scale). Using the intention to treat principle, ordinal, ratio, and categorical data will be analyzed using the Mann-Whitney, paired t-test, and Pearson’s chi-square, respectively and summarized using 95% confidence intervals. Assuming a standard deviation of 2 faces, 83 children per group will be required to detect a 1-face difference at 5% significance with 90% power. Increasing by 20% equals 100 participants per group. P values <0.05 will be considered significant. An institutional audit revealed 380 eligible patients per year during research assistant availability. Given a 30% refusal rate, we expect five participants enrolled per week for 40 weeks. Importance: Our findings will guide evidence-based analgesic choices for children with non-surgical abdominal pain in the ED.