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Objectives To compare the measurement properties of paediatric patient-reported outcome measures (P-PROMs) used in clinical trials and practice for common conditions.Design Data from the Australian Paediatric Multi-Instrument Comparison study were used, including children aged 5–18 years with autism spectrum disorder (ASD) (n=510), asthma (n=487), eating disorder(s) (n=216), epilepsy (n=298), recurrent abdominal pain (n=392), sleep problems (n=346), dental problems (n=490), type 1 diabetes (T1D) (n=67), enuresis (n=182) and no health conditions (reference group) (n=1259). The acceptability, response distribution (floor/ceiling effects), known-groups validity, test-retest reliability, responsiveness and convergent validity of the Paediatric Quality of Life Inventory (PedsQL), EuroQol Group’s Youth instruments with three and five response options (EQ-5D-Y-3L and EQ-5D-Y-5L), Child Health Utility 9D (CHU9D), Assessment of Quality of Life 6D (AQoL-6D), Health Utilities Index Mark 3 and Patient-Reported Outcomes Measurement Information System Paediatric Profile 25 (PROMIS-25) were assessed.Results PedsQL, EQ-5D-Y-3L, EQ-5D-Y-5L, CHU9D and PROMIS-25 were easy and quick to complete, indicating acceptability. Only the EQ-5D-Y-3L and EQ-5D-Y-5L demonstrated ceiling effect issues. All measures were able to differentiate between children with no health conditions and children with each condition (p<0.001, effect sizes between 0.47 and 3.5), indicating known-groups validity. Test-retest reliability varied by condition; however, the PedsQL and EQ-5D-Y-5L were the most reliable.Conclusions Certain P-PROMs may be preferred in different conditions, that is, ASD (PedsQL and EQ-5D-Y-5L), asthma (PedsQL), eating disorder(s) (PedsQL and CHU9D), epilepsy (PedsQL and CHU9D), recurrent abdominal pain (PedsQL, EQ-5D-Y-5L and CHU9D), sleep problems (PedsQL), dental problems (PedsQL), T1D (PedsQL and CHU9D) and enuresis (PedsQL). Notably, the PedsQL performed favourably in all conditions assessed. More evidence is required on the responsiveness of P-PROMs to changes in child health.Trial registration number ACTRN12621000657820.