The primary aim of this systematic review is to assess the effectiveness of evidence-based healthcare (EBHC) educational interventions on healthcare professionals' knowledge, skills, attitudes, behaviour of EBHC, clinical process and care outcomes. A secondary aim of the review is to assess the effects of important pedagogical moderating factors for EBHC educational interventions. This systematic review used a forward and backward citation search strategy on the Web of Science platform (date of inception to 28 April 2023). Only randomised controlled trials (RCTs) and cluster RCTs which compared EBHC educational interventions for healthcare professionals were included. A random effects meta-analysis was undertaken for EBHC compared with an active and nonactive control for all outcomes. Sixty-one RCTs were identified which included a total of 5208 healthcare professionals. There was a large effect for EBHC educational interventions compared with waiting list/no treatment/sham control on knowledge (SMD, 2.69; 95% CI, 1.26-4.14, GRADE Low), skills (SMD, 0.88; 95% CI, 0.25-1.73, Very Low Certainty), attitude (SMD, 0.81; 95% CI, 0.16-1.47, Very Low Certainty) and behaviour of EBHC (SMD, 0.82; 95% CI, 0.25-1.40, Very Low Certainty). Over time the effect of EBHC educational interventions substantially decreased with no evidence of effect at 6 months for any outcome except behaviour (SMD,1.72; 95% CI, 0.74-2.71, Low Certainty). There was some evidence that blended learning, active learning and consistency in the individual delivering the intervention may be important positive moderating factors. These findings suggest that EBHC educational interventions may have a large short-term effect on improving healthcare professionals' knowledge, skills, attitude and behaviour of EBHC. These effects may be longer-lasting regarding EBHC behaviour. In terms of pedagogy, blended learning, active learning, and consistency of the individual delivering the intervention may be important positive moderating factors.