Objective To compare the effectiveness and safety of prescribing ibuprofen and oxycodone for at-home management of children’s fracture pain. Methods A prospective observational cohort was conducted at the Stollery Children’s Hospital pediatric emergency department (June 2010-July 2014). Children aged 4–16 years with an isolated fracture discharged home with advice to use either ibuprofen or oxycodone were recruited. Results A cohort of 329 children (n = 217 ibuprofen, n = 112 oxycodone) were included. Mean age was 11.1 years (SD 3.5); 68% (223/329) were male. Fracture distribution included 80.5% (264/329) upper limb with 34.3% (113/329) requiring fracture reduction. The mean reduction in Faces Pain Score-Revised score (maximum pain–post-treatment pain) for Day 1 was 3.6 (SD 1.9) (ibuprofen) and 3.8 (SD 2.1) (oxycodone) (p = 0.50); Day 2 was 3.6 (SD 1.8) (ibuprofen) and 3.7 (SD 1.6) (oxycodone) (p = 0.56); Day 3 was 3.7 (SD 1.7) (ibuprofen) and 3.3 (SD 1.7) (oxycodone) (p = 0.24). Children prescribed ibuprofen (51.2%, 109/213) experienced less adverse events compared to those prescribed oxycodone (70.5% 79/112) on Day 1 (p = 0.001). Children prescribed ibuprofen (71.8%, 150/209) had their function (eat, play, school, sleep) affected less than those prescribed oxycodone (83.0%, 93/112) (p = 0.03) on Day 1. Conclusion Children prescribed ibuprofen or oxycodone experienced similar analgesic effectiveness for at-home fracture pain. Oxycodone prescribing was associated with more adverse events and negatively impacted function. Oxycodone use does not appear to confer any benefit over ibuprofen for pain relief and has a negative adverse effect profile. Ibuprofen appears to be a safe option for fracture-related pain.