Aim: To compare the efficacy of a standard NaOCl irrigation procedure with that of Er,Cr:YSGG laser irradiation in contaminated root canals having small and large apical foramina. Methodology: Forty root canals of extracted central incisor teeth with straight roots were chosen so that their apical foramina just permitted the tip of a size 20-K file to pass through. The canals were then enlarged with files to size 60 and randomly divided into four groups of 10 teeth each. The apical foramina of one group were widened further so that the tip of a size 45-K file could just pass through. After sterilization, all roots were inoculated with Enterococcus faecalis for 48 h at 37°C. The first group was used as a control, the second group was irrigated with 3% NaOCl solution for 15 min, and the last two groups having different sizes of apical foramina were irradiated with the Er,Cr:YSGG laser at output power from 0.5 W, with 20% air and water levels. The disinfecting efficacy of the groups was tested by collecting dentine chips from the inner canal walls of the specimens and counting viable E. faecalis on Mueller-Hinton agar plates. Results: The differences in the mean number of viable colonies between the control and laser groups were statistically significant (P < 0.05). The control specimens had the highest number of microorganisms (153 × 103 ± 39 × 103). Complete sterilization was achieved in the 3% NaOCl group. The mean colony forming units (CFU) values obtained after Er,Cr:YSGG laser irradiation were 6.6 × 103 CFU and 6.5 × 10 3 CFU in root canals having large and small apical foramina respectively. Conclusion: In teeth with straight roots the Er,Cr:YSGG laser reduced the viable microbial population in root canals with small and large apical foramina but did not eradicate all bacteria. Three percent NaOCl inhibited the growth of E. faecalis and effectively sterilized all root canals. © 2007 International Endodontic Journal.