Non-ergot dopamine agonists (NEDAs) have become the gold-standard agents for the treatment of restless legs syndrome (RLS). While the efficacy and safety of these drugs have been widely studied, their effect on patients' health-related quality of life (HRQoL) has not been fully elucidated. To better define the usefulness of NEDAs by assessing their impact on HRQoL. We performed a meta-analysis of randomized, double-blind, placebo-controlled trials evaluating the use of NEDAs in patients with RLS. A systematic literature search of MEDLINE, EMBASE, and Cochrane CENTRAL was performed from the earliest possible date through July 2008. Trials were included in the analysis if they evaluated NEDAs for the treatment of RLS and reported HRQoL using any RLS disease-specific HRQoL instrument. HRQoL data were pooled and evaluated using an inverse variance weighting approach as standardized mean differences (SMDs) and 95% confidence interval (CI). For trials reporting HRQoL data obtained using the Johns Hopkins RLS-QoL Questionnaire, adjusted mean difference data were pooled to calculate the weighted mean difference (WMD) and 95% CI. Seven trials (N = 1483) met all inclusion criteria. Patients with RLS taking NEDAs had significantly improved overall effect on HRQoL compared with those taking placebo (SMD 0.20; 95% CI 0.10 to 0.30; degree of inconsistency across studies [I(2)] = 0%). When analyzing trials using the Johns Hopkins RLS-QoL questionnaire, the results also showed improvement with NEDAs compared with placebo (WMD 4.72; 95% CI 2.96 to 6.47; I(2) = 0%). Study conclusions were unchanged upon sensitivity analysis. The number of trials for each NEDA was small, limiting the usefulness of between-agent comparisons. In patients with RLS, use of NEDAs showed improved HRQoL compared with placebo. Since pooled effect sizes observed in this meta-analysis appear to surpass accepted values for minimally important clinical differences, these improvements may be clinically relevant for the average studied patient. However, future studies evaluating long-term treatment of RLS with NEDAs are necessary, as are head-to-head comparative trials and economic assessments.