Tehran University of Medical Sciences Journal of Pharmaceutical Care 2322-4630 8 3 2020 09 28 116 122 Nioosha Yarahmadi Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Farshad Hashemian Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Reza Hosseini Doust Department of Microbiology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 2020 02 15 2020 05 09 Background:  Preparation of a new product with the goal of reducing chlorhexidine’s side effects without decreasing (and even increasing) its effectiveness is a desirable goal for researchers in the field of oral hygiene. The aim of this study was to evaluate the efficacy of Chlorhexidine 0.2% and Cetylpyridinium 0.05% combination in reducing oral bacteria in comparison with Chlorhexidine 0.2%, Cetylpyridinium 0.05% and Persica mouthwashes. Methods: 100 healthy volunteers aged between 18 and 30 years were randomly assigned to 5 groups. The first group received Chlorhexidine 0.2%, the second group received Cetylpyridinium 0.05%, the third received Persica, the fourth received Chlorhexidine 0.2% plus Cetylpyridinium 0.05%, and the fifth group received Chlorhexidine 0.05% plus Cetylpyridinium 0.05%. Samples were obtained at baseline and thirty minutes after oral rinsing with the mouthwashes. The number of colony-forming units (CFU/mL) before and after mouthwash administration was compared for each sample.   Results: The preparation with the most bacterial count reduction was found to be Chlorhexidine 0.2% and Cetylpyridinium 0.05% combination. However, the difference between efficacy of Chlorhexidine 0.2% plus Cetylpyridinium 0.05% and Chlorhexidine 0.05% plus Cetylpyridinium 0.05% was found not to be statistically significant. Conclusions: A new mouthwash preparation including chlorhexidine 0.05% and cetylpyridinium 0.05 % combination is the most desirable due to the increased efficacy and fewer side effects. https://jpc.tums.ac.ir/index.php/jpc/article/view/325