Background: Various interventions have been introduced to try to prevent suicides at suicide hotspots, but evidence of their effectiveness needs to be strengthened. Methods: We did a systematic search of Medline, PsycINFO, and Scopus for studies of interventions, delivered in combination with others or in isolation, to prevent suicide at suicide hotspots. We did a meta-analysis to assess the effect of interventions that restrict access to means, encourage help-seeking, or increase the likelihood of intervention by a third party. Findings: We identified 23 articles representing 18 unique studies. After we removed one outlier, interventions that restricted access to means were associated with a reduction in the number of suicides per year (incidence rate ratio 0.09, 95% CI 0.03-0.27; p<0.0001), as were interventions that encourage help-seeking (0.49, 95% CI 0.29-0.83; p=0.0086), and interventions that increase the likelihood of intervention by a third party (0.53, 95% CI 0.31-0.89; p=0.0155). When we included only those studies that assessed a particular intervention in isolation, restricting access to means was associated with a reduction in the risk of suicide (0.07, 95% CI 0.02-0.19; p<0.0001), as was encouraging help-seeking (0.39, 95% CI 0.19-0.80; p=0.0101); no studies assessed increasing the likelihood of intervention by a third party as a lone intervention. Interpretation: The key approaches that are currently used as interventions at suicide hotspots seem to be effective. Priority should be given to ongoing implementation and assessment of initiatives at suicide hotspots, not only to prevent so-called copycat events, but also because of the effect that suicides at these sites have on people who work at them, live near them, or frequent them for other reasons. Funding: National Health and Medical Research Council, Commonwealth Department of Health.