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Background and Aim: Due to the increasing use of restorative materials, finding a suitable material with low adhesion rate and colonization of pathogenic Streptococcus mutans has a significant importance. The purpose of this study was the comparison of the adhesion rate of Streptococcus mutans to "Nano-hybrid composite" and "Amalgam" at 1, 3, and 7 day intervals. Methods and Materials: In this experimental study, 72 samples of Amalgam and composite resin were placed in two equal groups and exposed to bacterial suspension holding 1× 10 6 cell/ml and after three time periods of 1, 3, and 7 days, the restorative material samples were suspended in 1cc of physiologic serum, and 100µl of the suspension was cultured on Blood Agar medium. After 48 hours the number of Streptococcus mutans colonies were counted. The data were analyzed by T-test. Results: The mean and standard deviation of Streptococcus mutans colonies adhered to Nano-hybrid composite resin at 1, 3, and 7 day intervals were measured 12.7±2.3, 1.5±2.12 and zero colonies, respectively. Adherence of Streptococcus mutans to composite resin during these three days, showed a significant statistical difference (p<0.005). The mean and standard deviation of colonies, which adhered to Amalgam at 1, 3 and 7 day intervals were 32±7.01, 18.8±3.8 and zero colonies, correspondingly. The adherence of Streptococcus mutans to Amalgam during these three days showed a significant statistical difference (p<0.001). The comparison between Amalgam and composite resin showed that the adherence of Streptococcus mutans to composite resin was lower during the first and the third day and the results were statistically significant (p<0.001). Conclusion:The result of this study showed that adhesion of Streptococcus mutans to Nano-hybrid composite is lower than the adhension to Amalgam. Conclusion:The results indicated that adhesion of Streptococcus mutans to Nano-hybrid composite is lower than the adhesion to Amalgam.