Experimental bristle arrangements were applied to a conventional V-shaped bristle-design toothbrush in an effort to improve plaque removal efficacy in interproximal areas. A single-blind cross-over study was performed to evaluate the plaque removal efficacy of this new bristle arrangement by comparing it to either a more conventional V-shaped toothbrush or a flat-headed toothbrush. Plaque removal efficacy was determined by assessing the percentage of plaque score reduction following a single controlled brushing. The new toothbrush bristle arrangement had a significantly higher plaque removal percentage efficacy than both the V-shaped toothbrush (59.1% vs. 48.5%; p = 0.0092) and the flat-headed toothbrush (65.3% vs. 55.3%; p = 0.0260) in interproximal areas. These differences were also consistent with whole mouth comparisons. When the subjects were asked about their preferences for the three different bristle formats used in this study, there was no significant difference of opinion found. These findings indicated a superiority of the new toothbrush to the other two, more conventional toothbrush bristle styles on plaque removal efficacy with these study subjects, but no particular preference for bristle design.