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Objective: The aim of this systematic review was to establish the effectiveness of brushing with a triple-headed manual toothbrush compared to a single-headed manual toothbrush on plaque removal., Materials and Methods: The MEDLINE-PubMed and Cochrane-CENTRAL databases were searched. The inclusion criteria were clinical trials conducted with humans without fixed orthodontic appliances who were not dental care professionals. Papers that evaluated the effect of toothbrushing with a triple-headed manual toothbrush compared to a single-headed manual toothbrush on plaque removal were included. Data were extracted from the eligible studies, and a descriptive analysis was performed., Result: The search retrieved 15 eligible publications including 18 relevant comparisons. Heterogeneity was most obvious with respect to the person who performed the brushing, either the participants themselves or a caregiver responsible for daily oral hygiene. Additionally, participant characteristics such as age and individual disabilities varied. A lack of appropriate data and a variation in the indices used allowed only a descriptive analysis. Of the 14 comparisons with self-performed brushing by the participants, the majority showed no difference between triple-headed and single-headed toothbrushes, with a few favouring the triple-headed. In the comparisons in which a caregiver performed the brushing, three of the four showed that the triple-headed toothbrush performed significantly better on the reduction in plaque scores., Conclusion: From this review emerges the recommendation that the use of a triple-headed manual toothbrush instead of a single-headed manual toothbrush might be favorable with respect to plaque removal in case a care-dependent individual is brushed by a caregiver., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)