Despite widespread scientific and popular interest in mindfulness-based interventions, questions regarding the empirical status of these treatments remain. We sought to examine the efficacy of mindfulness-based interventions for clinical populations on disorder-specific symptoms. To address the question of relative efficacy, we coded the strength of the comparison group into five categories: no treatment, minimal treatment, non-specific active control, specific active control, and evidence-based treatment. A total of 142 non-overlapping samples and 12,005 participants were included. At post-treatment, mindfulness-based interventions were superior to no treatment (d = 0.55), minimal treatment (d = 0.37), non-specific active controls (d = 0.35), and specific active controls (d = 0.23). Mindfulness conditions did not differ from evidence-based treatments (d = − 0.004). At follow-up, mindfulness-based interventions were superior to no treatment conditions (d = 0.50), non-specific active controls (d = 0.52), and specific active controls (d = 0.29). Mindfulness conditions did not differ from minimal treatment conditions (d = 0.38) and evidence-based treatments (d = 0.09). Effects on specific disorder subgroups showed the most consistent evidence in support of mindfulness for depression, pain conditions, smoking, and addictive disorders. Results support the notion that mindfulness-based interventions hold promise as evidence-based treatments.