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The purpose of this study was to assess the seal obtained in straight and curved root canals filled with either laterally compacted gutta-percha or Thermafil obturators. Each technique was used in combination with three different sealers (RSA RoekoSeal, AH Plus, AH 26). Thermafil obturators were also used without sealer, resulting in a total of 14 test groups of 16 teeth each. Sixty teeth served as positive or negative controls. Included in the study were 142 extracted teeth with straight and 142 with curved root canals. All canals were enlarged up to size 40. After obturation, all roots were placed in India ink for 48 h and rendered transparent to measure the maximum linear dye penetration. Canals filled with Thermafil obturators had significantly more extrusion of filling material than canals filled by lateral compaction (p < 0.01). Thermafil without sealer showed significantly greater dye penetration compared with all other groups both in straight and in curved canals (p < 0.05). As long as a sealer was used, the seal obturated with Thermafil was equivalent in terms of dye penetration to lateral compaction. There were no statistical differences in the mean apical dye penetration among the three sealers. The differences between the dye penetration in straight and in curved canals were insignificant for all groups (p > 0.05). Under the conditions of this study, Thermafil obturators achieved seals comparable to lateral compaction, as long as a sealer was used.