Purpose: Head-to-head comparison of reliability, validity and responsiveness of four patient-reported outcome measures (PROMS) suitable for assessing health-related quality of life (HRQOL) in palliative care settings: EORTC QLQ-C15-PAL, FACT-G7, FACIT-Pal and short-form FACIT-Pal-14. Methods: Secondary analysis of two phase III randomised trials: ketamine for chronic cancer pain, octreotide for vomiting in inoperable malignant bowel obstruction. Sub-groups were defined by Australia-modified Karnofsky performance status (AKPS) and participants��� global impression of change (GIC). Two aspects of reliability were assessed: internal consistency (Cronbach alpha, ��); test���retest reliability (intra-class correlation coefficient (ICC)) of patients with stable AKPS and those who self-reported ���no change��� on GIC. Construct validity was assessed via pre-determined hypotheses about sensitivity of PROM scores to AKPS groups and responsiveness of PROM change scores to GIC groups using analysis of variance. Results: FACIT-Pal had better internal consistency (�� ranged 0.59���0.80, 15/18 ��� 0.70) than QLQ-C15-PAL (0.51���0.85, 4/8 ��� 0.70) and FACT-G7 (0.54���0.64, 0/2 ��� 0.70). FACIT scales had better test���retest reliability (FACIT-Pal 11/27 ICCs ��� 0.70, FACT-G7 2/3 ICCs ��� 0.70) than QLQ-C15-PAL (2/30 ICCs ��� 0.70, 18/30 ��� 0.5). Four scales demonstrated sensitivity to AKPS: QLQ-PAL-15 Physical Functioning and Global QOL, FACT-G Functional Wellbeing and FACIT-Pal Trial Outcome Index (TOI). Nine scales demonstrated responsiveness: three in the ketamine trial population (QLQ-C15-PAL Pain, FACIT-Pal-14, FACT-G7), six in the octreotide trial population (QLQ-C15-PAL Fatigue; FACIT-Pal PalCare, TOI, Total; FACT-G Physical Wellbeing and Total). Conclusions: No PROM was clearly superior, confirming that choosing the best PROM requires careful consideration of the research goals, patient population and the domains of HRQOL targeted by the intervention being investigated.