Aim:The aim of this study is to compare the corono-apical sealing ability of three single-cone obturation systems using a glucose leakage model.Materials and Methods:A total of 90 extracted maxillary single rooted teeth were selected and their crowns were cut. The root canal of each sample was instrumented using a rotary crown down technique and then divided into four experimental (n = 20 each) and two control groups (n = 5 each). Samples in the experimental groups were filled as follows: Group 1, cold lateral condensation using Gutta-percha/AH Plus; Group 2, single-cone Gutta-percha and AH Plus; Group 3, single-cone Gutta-percha/and GuttaFlow2; Group 4, single-cone Resilon/RealSeal SE after 7 days, the sealing ability of root canal fillings was tested at different time intervals using glucose leakage model. Glucose leakage values were measured using a spectrophotometer and statistically analyzed.Results:The four experimental groups presented significantly different glucose leakage values at all test periods (P < 0.05). At the end of the observation period, the cumulative glucose leakage values of Groups 3 and 4 were significantly lower than those of Groups 1 and 2 (P < 0.05).Conclusion:Gutta-percha/GuttaFlow2 or Resilon/RealSeal SE combinations provided the superior sealing ability over the lateral condensation technique.