Two independent studies were conducted to evaluate and compare the clinical performance of two commercially available manual toothbrushes (Colgate Total Professional and the Oral-B Cross Action). Study I was a short-term, examiner-blind crossover clinical trial (N = 30) designed to measure the removal of 24-hour plaque build-up. All subjects refrained from brushing for 24 hours and were screened for dental plaque on the facial and lingual surfaces of all natural teeth using the Rustogi Modified Navy Plaque Index. Patients then received one of the two study toothbrushes and brushed their teeth for a timed one minute. They were then re-assessed for plaque. The data showed that the Colgate Total Professional toothbrush performed better than the Oral-B Cross Action toothbrush in reducing whole-mouth plaque scores (p < 0.001). Study II was a definitive six-week, single-blind clinical trial (N = 55), conducted in harmony with American Dental Association guidelines, to assess the ability of the two toothbrushes to reduce supragingival plaque and gingivitis. In this study, the subjects were stratified into two balanced groups based on their baseline plaque and gingivitis scores. Subjects were then instructed to continue with their normal brushing technique twice daily for one minute with their assigned toothbrush and a commercially available dentifrice. Examinations for plaque (Rustogi Modified Navy Plaque Index), and gingivitis (Loe-Silness Gingival Index) were conducted by the same examiner at baseline, after three weeks, and again after six weeks. The data from this long-term clinical trial showed that the Colgate Total Professional toothbrush exhibited statistically significantly lower plaque and gingivitis scores than did the Oral-B Cross Action toothbrush. The magnitudes of these differences were 29.5% for plaque and 31.1% for gingivitis. These reductions are adequate to support the claim that the Colgate Total Professional toothbrush provides clinically superior control of supragingival plaque and gingivitis, when studied in accordance with the criteria provided by the 1999 Guidelines of the American Dental Association for determining superiority.