One of the key design features that determine the efficacy of a powered toothbrush is the manner in which the bristled portion of the brush head is activated. Objective: The objective of this study was to compare the plaque reduction efficacy and safety of a prototype sonic toothbrush in which the brush head moves in a twisting motion (prototype) to a Sonicare® (Philips Oral Healthcare Inc.) which has a sweeping motion (control). Method: An examiner-blinded, randomized crossover study was conducted with 12 healthy adults. Subjects meeting the entrance criteria were disclosed and screened for plaque using the Turesky modification of the Quigley-Hein Plaque Index. Subjects with an index of at least 1.9 following 12 to 16 hours of oral hygiene abstinence were entered into the study. The subjects were randomized into one of two treatment groups and brushed for two minutes with the control toothbrush and for two minutes with the prototype brush. Following a period of 24 hours without oral hygiene, subjects were disclosed and scored for plaque. After brushing with a randomly selected device, an intraoral examination was performed. Subjects were disclosed again and re-evaluated for post-brushing plaque, after which they brushed for an additional two minutes with the control device. Three more evaluations were conducted, each within 24 hours of the last using the same procedures, resulting in each device being used twice. Results: The improvement of the prototype over the control was 16%, 16%, and 20% for the overall, interproximal, and posterior regions, respectively. No soft tissue abnormalities were noted with either brush. Analysis of variance showed the difference between the two brushes was statistically significant at the 95% confidence level for each region. Conclusion: The prototype sonic toothbrush with the twisting motion achieved statistically superior plaque reduction as compared to the control toothbrush (p<0.05).