Objectives: The aim of this paper is to evaluate the influence of the internal anatomy on the leakage of root canals filled with the thermoplastic technique. Materials and methods: The upper central incisors (UCI) and mesial roots of the lower molars (MRLM) (n = 12 each) were tested regarding leakage using the gas-enhanced permeation test (GEPT) after root filling. The quality of the root fillings was assessed using micro-computed tomography (μCT) by superimposing scans before and after treatment to calculate unfilled volume. The calculated void volume was compared between the groups and correlated to the measured leakage values. Data were analyzed using t test and Pearson’s correlation tests (p < 0.05). Results: The mean void volume did not differ between UCI and MRLM (13.7 ± 6.2% vs. 14.2 ± 6.8%, respectively). However, significantly more leakage was evident in the MRLM (p < 0.001). While the leakage correlated highly to the void volume in the MRLM group (R2 = 0.981, p < 0.001), no correlation was found in UCI (R2 = 0.467, p = 0.126). Conclusion: MRLM showed higher leakage values, which correlated to the void volume in the root canal fillings. Clinical relevance: Care should always be taken while doing root canal treatments, but attention to teeth with known/expected complex root canal anatomy should be considered. © 2017, Springer-Verlag GmbH Germany.