Background: Mental Health First Aid (MHFA) has received substantial international attention since its founding in the late 1990s, with a growing evidence base relating to its nature and impact across a variety of settings. Aims: To identify the effectiveness of MHFA upon a range of outcomes, recipients, its cost-effectiveness, and the mechanisms of its effect.Method: A systematic evidence synthesisResults: Data from 65 studies show MHFA education improves trainees’ mental health literacy, their perceived confidence in helping people living with mental distress and their intentions to help such people. MHFA also raises employees’ knowledge of mental illnesses in the workplace. There was also evidence of MHFA trainees using aspects of the five-stage ALGEE MHFA approach in their helping behaviour. The quality of the studies in this review varied across different types of studies. No published studies to date have evaluated MHFA’s impact on recipient outcomes, articulated the mechanisms of its effect, its cost-effectiveness, or societal impact.Conclusions: MHFA remains popular, but evidence of its effectiveness upon those receiving it remains unknown. It is urgent to undertake studies testing the effectiveness and cost-effectiveness of MHFA upon recipients, as well as identifying, empirically, how MHFA works, for whom, under what conditions, and barriers to its implementation. Given that the enthusiasm and acceptance of MHFA appears widespread, systematic evaluations of its social impact are warranted.Registration: The review protocol has been submitted to the Open Science Framework (View-only link: https://osf.io/rj4uh/?view_only=d1f9f2ed73724b3f8075c0c4581d0d87).