Waterpipe smoking has become a global youth trend especially in the Middle East countries and Iran . The aim of this study was to determine the mutagenic effects of three most popular flavored tobaccos by four different salmonella typhimurium strains and compare the possible mutagenic effects of the test samples. Ames mutagenicity assessment was conducted according to the OECD guideline using TA100, TA98 , YG1024 and YG1029 strains. Charcoal burned flavored tobaccos of three different flavors including Orange, Double Apple, and Lime Mint were filtered and exposed to all strains after strain identification tests and MIC ,MBC determinations. The Ames test results indicated significant mutagenic effects of tobacco samples in all four test strains when compared with negative control (p≤0.0001). The highest Mutagenic Factor (MF) was seen in Double Apple samples using TA 98 (MF=11.5±3.3) . In all experiments, TA strains showed higher sensitivity to the samples than YG strains which suggest these two strains for further regulatory toxicity tests ,policy making purposes and tobacco control programs . Present results represents an important step in understanding the genotoxic potentials of three most popular flavored tobaccos samples of a famous brand in the global markets .