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Previous literature has shown that multifaceted, interactive interventions may be the most effective way to train health and social care professionals. A Train-the-Trainer (TTT) model could incorporate all these components. We conducted a systematic review to determine the overall effectiveness and optimal delivery of TTT programs.We searched 15 databases. Reference lists and online resources were also screened. Studies with an objective follow-up measure collected over 1 week after the intervention were included. The intervention had to be based on a TTT model for health and social care professionals.Eighteen studies met the inclusion criteria. TTT interventions varied greatly, ranging from didactic presentations to group discussions and role-plays. The heterogeneity of the studies and limited data prevented metaanalysis. A narrative review found that the TTT programs in 13 studies helped to increase knowledge, improve clinical behavior, or produce better patient outcomes. One study showed no effect. Three studies showed possible effect and one study showed that a CD-ROM training method was more effective than a TTT training method in improving participants' knowledge. Ratings of the studies' methodologies suggested moderate risk of bias, which limits interpretation of the results.There is evidence that using a blended learning approach to deliver TTT programs—combining different techniques such as interactive, multifaceted methods and accompanying learning materials—can help to effectively disseminate and implement guidelines and curricula to health and social care professionals. However, further research is needed to determine the optimum “blend” of techniques.