Abstract Ninety-two dental and dental hygiene students completed a double-blind, controlled clinical trial. The purpose of the trial was to evaluate the effects of toothpastes, in varying concentrations of flavor and tartar-control agents. Four formulations of toothpastes were assessed: (A) control—low flavor with no tartar control; (B) medium flavoring with medium tartar control; (C) high flavoring with medium tartar control; and (D) medium flavoring with no tartar control. Soft tissue reactions were assessed objectively and independently by three examiners. Subjective perceptions about each toothpaste were gathered by a structured, open-ended questionnaire. The “tartar control” toothpastes, B and C, resulted in statistically significant ( p < 0.005) higher rates of mucosal reactions (e.g., ulceration, sloughing, erythema, migratory glossitis) than the “non-tartar control” toothpastes A and D. When the oral mucosal reaction rates were adjusted for multiple clinical observations within each subject at the same point in time there was no statistically significant ( p > 0.05) difference between male (0.25) and female (0.28) subjects. In this study population, the order of preference was observed as toothpaste A>D>B>C. The major reasons for disfavor were burning sensation in toothpastes C (2.4%) and B (4%).