Background: This systematic review evaluated the effectiveness of distraction for reducing infant distress during vaccinations in young children aged 0 to 3 years. Design/Methods: Database searches identified relevant randomized and quasi-randomized controlled trials. Three separate clinical questions related to variants of the psychological strategy of distraction (directed video; directed toy; nondirected toy) were pursued. Distress was identified as the critical outcome to assess the benefits of distraction and extracted from relevant trials. Distress was analyzed by phase of procedure (distress preprocedure; distress acute; distress recovery; idiosyncratic phases based on some or all of the 3 aforementioned phases). Results: Ten studies were included in the review. Significant results are presented herein. For directed video distraction, moderate quality evidence suggested that distress was lowered in the treatment group standardized mean difference (SMD -0.68 lower [95% confidence interval (CI), -1.04 to -0.32]) for the acute+recovery phase as well as the preprocedure phase (SMD -0.49 lower [95% CI, -7.6 to -0.22]). For directed toy distraction, the analysis of low-quality evidence for a combined preprocedure+acute+recovery phase of distress (analysis n=81), suggested that distress was lowered in the treatment group (SMD -0.47 lower [95% CI, -0.91 to -0.02]). An effect for nondirected toy distraction was also seen, analyzing very-low-quality evidence, for the acute distress phase (n=290; SMD -0.93 lower [95% CI, -1.86 to 0.00]). Conclusion: Generally low-quality to very-low-quality evidence suggests that there may be an effect of directed (toy and video) and nondirected toy distraction for children aged 0 to 3 years, for certain phases of the vaccination.