Background: Paediatric imaging often requires sedation to minimize movement and obtain diagnostic-quality images. Midazolam and ketamine are commonly used agents, but their comparative efficacy, recovery characteristics, and safety profiles may differ.Methods: A prospective comparative observational study was conducted from August 2025 to April 2026 among 240 paediatric patients requiring sedation for diagnostic imaging. Participants were equally allocated to a midazolam group (n = 120) and a ketamine group (n = 120). The primary outcome was successful completion of imaging without significant movement or rescue sedation. Secondary outcomes included time to adequate sedation, recovery time, physiological stability, and sedation-related adverse events.Results: Successful imaging completion was achieved in 105 (87.5%) patients in the midazolam group and 113 (94.2%) in the ketamine group, although the difference was not statistically significant (p = .071). Ketamine produced a significantly faster onset of adequate sedation than midazolam (6.9 ± 2.1 vs. 8.6 ± 2.4 minutes; p < .001). Recovery was significantly shorter with midazolam (38.4 ± 9.7 vs. 43.7 ± 10.8 minutes; p < .001). Oxygen desaturation occurred in 4.2% and 2.5% of patients, respectively (p = .475)Conclusion: Both midazolam and ketamine provided effective and clinically acceptable sedation for paediatric imaging. Ketamine offered faster sedation onset, whereas midazolam provided faster recovery, supporting individualized sedative selection based on patient and procedural requirements.