Abstract Context The Research Prioritization Task Force (RPTF) of the National Action Alliance for Suicide Prevention (Action Alliance) conducted a comprehensive literature review of suicide prevention/intervention trials to assess the quality of the scientific evidence. Evidence acquisition A literature “review of reviews” was conducted by searching the most widely used databases for mental health and public health research. The quality of the reviews was evaluated using the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) system; the quality of the scientific evidence for the suicide preventions/interventions was assessed using U.S. Preventive Services Task Force (USPSTF) criteria. The reviews were limited to peer-reviewed publications with human subjects published in English. Evidence synthesis Ninety-eight systematic reviews and 45 primary sources on suicide prevention/interventions published between January 2000 and September 2012 were evaluated. The results suggest that the quality of both the systematic reviews and the scientific evidence for suicide preventions/interventions were mixed. The majority of the systematic reviews and prevention/interventions were evaluated as fair to poor in quality. Conclusions There are many promising suicide prevention/intervention trials, but research findings are often inconclusive because of methodologic problems. Methodologic problems across systematic reviews include not conducting hand searches, not surveying grey literature, and being unable to aggregate data across studies. Methodologic problems with the scientific quality of the prevention/intervention trials include paucity of information on sample demographic characteristics, poorly defined outcomes, and excluding actively suicidal participants. Suggestions for ways to improve the quality of the systematic reviews and suicide preventions/interventions are provided.