OBJECTIVE The purpose of this clinical study was to evaluate the efficacy in reducing dental plaque regrowth of two mouthwashes containing 0.075% cetylpyridinium chloride (CPC), one with 6% alcohol and one alcohol-free, as compared to a negative control mouthwash without CPC, using the Modified Gingival Margin Plaque Index (MGMPI). METHODS The study was a double-blind, randomized, three-way crossover, controlled design. Following a washout period, subjects reported to the dental clinic where they were instructed to brush their teeth, used their assigned mouthwash, and were scored by the examining dentist for plaque using the MGMPI method. Subjects were instructed to refrain from all oral hygiene for the next 24 hours, except for rinsing with their assigned mouthwash 12 hours post-brushing. After this 24-hour period, subjects returned to the dental clinic and were once again scored for plaque. This sequence of washout followed by mouthwash use and plaque scoring was repeated until each subject had used all three mouthwashes. An ANOVA was conducted to assess between-group differences. RESULTS The two test mouthwashes significantly reduced plaque regrowth over a 24-hour period (p < 0.05) as compared to the negative control mouthwash. The difference between the CPC-containing mouthwashes was not significant (p = 0.4868). CONCLUSIONS Two mouthwashes containing 0.075% CPC, one with 6% alcohol and the other alcohol-free, were found to be safe and effective in reducing plaque accumulation when compared a negative control mouthwash without CPC. In short-term studies, the MGMPI appears useful for evaluating the antiplaque efficacy of mouthwash products.