Objective: The primary aim was to estimate the pooled mean score of quality of life (QoL) (total, mental and physical health components) among patients with Restless Legs Syndrome (RLS).

Secondary aims were to assess: (I) QoL differences for RLS vs. control groups, (II) heterogeneity and possible sources; and (III) moderating variables.

Methods: Studies identified in PubMed, Scopus, Web of Science, and ProQuest between January 2000 and December 2022 were included. Methodological quality was assessed with Newcastle Ottawa Scale. The protocol was pre-registered (PROSPERO, CRD42023387318).

Results: Twenty-seven studies (20121 participants, 12 countries) were included. The corrected pooled estimated mean score of QoL was 47.92 (27 studies, CI 95 %: 43.11 to 52.72, range 0–100, i.e., low–high QoL) and was marginally affected by publication year (increased 0.89 by each year, p = 0.12). The corrected pooled estimated mean score of the mental health component was 47.32 (17 studies, 95 % CI: 43.12 to 51.51, range 0–100) and influenced by RLS instrument (decreased with recent versions, p = 0.05). The corrected pooled estimated mean score of the physical health component was 39.08 (17 studies, 95 % CI: 33.05 to 45.10, range 0–100), with no statistically significant moderator. The pooled estimated QoL scores were statistically significantly lower in RLS patients compared to control groups with standardized mean difference (SMD) of −0.78, −0.57 and −0.50 respectively for overall QoL (24 studies), physical and mental health components (14 studies). Total QoL SMD was affected by proportion of women.

Conclusion: Low QoL was revealed among RLS patients, which was statistically significantly reduced compared to control groups.