OBJECTIVES: In mental health, there are concerns that generic preference-weighted health-related quality of life (HRQoL) measures are not appropriate. Newer measures developed specifically for mental health are available. The aim of this systematic review and meta-analysis was to examine the impact of choice of HRQoL measure on decision-making. METHODS: We searched electronic databases to identify studies from OECD countries reporting health utilities, quality-adjusted life years (QALYs), or incremental cost-effectiveness ratios (ICERs) from two or more preference-weighted HRQoL measures for mental health populations. We summarised identified literature and completed random-effects meta-analyses for within-country comparisons. RESULTS: We identified 71 studies that reported head-to-head comparisons of HRQoL measures. We observed differences between EQ-5D and ReQoL both at baseline and change from baseline and some studies show differences between other measures. These differences can translate into substantial differences in incremental QALYs and ICERs that could influence decision-making. CONCLUSION: A substantial body of literature provides head-to-head comparisons of HRQoL measures and suggests that there can be important differences between HRQoL measures. Our findings contribute to the discussion around appropriateness of HRQoL measures for mental health populations and do not support changing from EQ-5D as a preferred HRQoL measure for HTA bodies, including NICE, for evaluations in adult mental health. Researchers should consider exploring the impact of HRQoL measures on under-researched populations and ensure comparisons for relevant outcomes are included in validation of new HRQoL measures.