Present study was conducted with the aim of evaluating antimicrobial efficacy of silver (AgNP) and gold nanoparticles (AuNP) with and without Nd: YAG laser (L) irradiation against experimentally inoculated Enterococcus faecalis in infected human root dentin. 120 extracted single rooted human teeth were prepared and inoculated with E. faecalis for 24 hrs. The teeth were then randomly divided into 4 experimental group: AgNPs group: irrigation for 3minutes with 50 ?l of 100 ppm, the AuNPs group: irrigation with 50 ?l of 100 ppm, the AgNPs & Nd: YAG lasers group: irrigation with 50 ?l of 100 ppm + irradiation with 1.5W laser for 60 seconds, the AuNPs & Nd: YAG lasers group: irrigation with 50 ?l of 100 ppm + irradiation with 1.5W laser for 60 seconds. One control group consisting of 2% CHX irrigation for 3 minutes was also there (n = 20). The specimens were collected from the canal before and after irrigation, and colony forming units were observed. Significant difference was found among all the groups in comparison to the control group (p<0.05). The greatest reduction in CFU?s was observed with combination of AgNPs & Nd: YAG lasers group. AgNPs in combination with Nd: YAG laser irradiation has the potential to be used as root canal disinfectant.