Background: There are now a substantial number of controlled trials investigating the efficacy of acceptance and commitment therapy (ACT). This meta-analysis combined multiple well-controlled studies to help clarify the overall impact of ACT relative to waiting lists, psychological placebos, treatment as usual, and established therapies. Method: A comprehensive literature search produced 18 randomized controlled trials (n = 917) that were included in the final analyses. Effect size was computed with Hedges’s g which can be interpreted with Cohen’s convention of small (0.2), medium (0.5), and large (0.8) effects. Results: There was a clear overall advantage of ACT compared to control conditions (effect size = 0.42). The average ACT-treated participant was more improved than 66% of the participants in the control conditions. Analyzed separately ACT was superior to waiting lists and psychological placebos (effect size = 0.68) and treatment as usual (effect size = 0.42). However, ACT was not significantly more effective than established treatments (effect size = 0.18, p = 0.13). Also, ACT was not superior to control conditions for the distress problems (anxiety/depression: effect size = 0.03, p = 0.84). Conclusions: The results reveal that ACT is more effective than control conditions for several problem domains, but there is no evidence yet that ACT is more effective than established treatments.