We conducted a prospective, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy of chlorhexidine gluconate/benzydamine HCl mouth spray for reducing pain and improving quality of life in patients with acute viral pharyngitis. Prior to treatment, patients rated the intensity of their pain on a visual analog scale and evaluated their quality of life on the 36-Item Short-Form Health Survey. Patients were then randomized to receive either paracetamol (acetaminophen) plus chlorhexidine/benzydamine or paracetamol plus placebo for 7 days. On days 3 and 7 of treatment, the participants again rated the intensity of their pain, and on day 7, they again rated their quality of life. A total of 164 patients were evaluable at study's end-80 in the chlorhexidine/benzydamine group and 84 in the control group. A comparison of self-evaluations revealed that the active treatment group reported less pain on both day 3 (p < 0.001) and day 7 (p = 0.002). Likewise, the chlorhexidine/benzydamine group reported a significantly better quality of life on day 7 (p < 0.001). Chlorhexidine/benzydamine was well tolerated, and no serious adverse events were observed.