Melodic Intonation Therapy (MIT) is a prominent rehabilitation program for individuals with post-stroke aphasia. Our meta-analysis investigated the efficacy of MIT while considering quality of outcomes, experimental design, influence of spontaneous recovery, MIT protocol variant, and level of generalization. Extensive literature search identified 606 studies in major databases and trial registers; of those, 22 studies-overall 129 participants-met all eligibility criteria. Multi-level mixed- and random-effects models served to separately meta-analyze randomized controlled trial (RCT) and non-RCT data. RCT evidence on validated outcomes revealed a small-to-moderate standardized effect in noncommunicative language expression for MIT-with substantial uncertainty. Unvalidated outcomes attenuated MIT's effect size compared to validated tests. MIT's effect size was 5.7 times larger for non-RCT data compared to RCT data (g̅ case report = 2.01 vs. g̅ RCT = 0.35 for validated Non-Communicative Language Expression measures). Effect size for non-RCT data decreased with number of months post-stroke, suggesting confound through spontaneous recovery. Deviation from the original MIT protocol did not systematically alter benefit from treatment. Progress on validated tests arose mainly from gains in repetition tasks rather than other domains of verbal expression, such as everyday communication ability. Our results confirm the promising role of MIT in improving trained and untrained performance on unvalidated outcomes, alongside validated repetition tasks, and highlight possible limitations in promoting everyday communication ability., (© 2022 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)