Objective To assess efficacy of a mouthwash containing 0.1% cetylpiridinium on gingivitis and plaque and its safety. Methods Multi-center randomized double-blind trial with positive control and split-mouth comparison was designed. Scaling on teeth of left side were conducted at do then on those of right side at D8. The cases rinsed five times a day in same way with assigned agents. Efficacy was measured using before-after differences of clinical and microbial variables. Re-examinations were scheduled at D4 and D8. Brushing was refrained between D0 and D4, resumed between D4 and D8. Results There were 144 patients with gingivitis included, 4 lost follow up. Data of 69 cases in test group and 71 in control group could be analyzed. Baseline data analysis showed that distributions of sex, age and values of clinical and microbial variables in both groups were well comparable. At D4 plaque accumulations of the scaled side in both groups were in same level, and Gingival index (GI), sulcus bleeding index (SBI) and VAS for halitosis were significantly reduced. At D8 the measurements of plaque index (PI), GI, SBI and VAS of halitosis decreased significantly more than those of D4. More than half of the suspected pathogenic strains were eliminated and log value of its CFU/ml decreased significantly but at same level in both groups. The balance of intra-oral bacterial flora was not disturbed. Seventeen cases in test group (24.6%) had minor and transient adverse reactions related to the mouthwash. Antimicrobial tests in vitro confirmed that the test agent could kill or inhibit growth of the pathogenic bacteria involving with oropharyngeal infection, gingivitis, periodontal diseases and caries. Conclusion The mouthwash containing cetylpiridinium could inhibit plaque, reduce severity of gingivitis and halitosis, with acceptable minor adverse reactions, similar to those of the marketed cetylpiridinum solution.