Objective: The study aimed to test the sensitivity of digital plaque imaging in distinguishing the effectiveness of test and control mouthwashes for different groups of tooth surfaces.Methods: The study was a double-blind, parallel, randomized, controlled clinical trial. Sixty subjects underwent scaling and polishing after recruitment, and attended their baseline examination after a washout phase of a minimum of seven days. They were then randomly assigned to one of two mouthwashes: 1) 0.05% CPC mouthwash; and 2) matching placebo mouthwash without CPC. Both groups were asked to use their assigned mouthwash and to refrain from any other oral hygiene measures for a period of eight days. At the baseline and day 8 visits, digital images of tooth surfaces were captured using Quantitative Light-induced Fluorescence (QLF™) imaging, and plaque area as a percentage of the tooth surface was measured. Comparisons were carried out between the products for different groups of tooth surfaces. The data generated by the software were validated by a manual plaque outlining technique.Results: Fifty-eight (58) subjects completed the study. More plaque was detected on the facial surfaces for the whole mouth (42.88% coverage for CPC and 46.45% for placebo) than the whole mouth lingual surfaces (7.23% coverage for CPC and 11.10% for -lacebo). Significant differences were observed between the products for the following areas: all tooth surfaces (p = 0.032), anterior lingual (p = 0.005), posterior lingual (p = 0.003), and whole mouth lingual (p = 0.001), whereas there were no differences between the products for anterior facial, anterior (facial & lingual), posterior facial, posterior (facial & lingual), and whole mouth facial. A strong correlation (R = 0.793, p < 0.001) was observed between the data (mean difference of percentage plaque coverage) generated by the analyzing program and that from the manual plaque outlining technique. Conclusion: The digital plaque imaging system was able to distinguish between the products when looking at the whole mouth. Digital imaging was better able to separate the groups when examining the lingual surfaces than facial.