Introduction: The purpose of this study was to evaluate dentinal tubule penetration (DTP) of calcium hydroxide (CH) and triple antibiotic paste (TAP) when performed with distilled water (DW) or a low surface tension liquid (ie, propylene glycol [PG]). Methods: Root apices of 40 single-rooted premolars were removed to obtain 14-mm roots in length. Root canals were enlarged to simulate immature teeth. After smear layer removal, the roots were randomly divided into 4 groups (n = 10) according to the root canal medicaments and the vehicles used: group 1:TAP + DW, group 2: TAP + PG, group 3: CH + DW, and group 4:CH + PG. Root canal medicaments were labeled with 0.1% rhodamine and applied into the canals using a Lentulo spiral. Specimens were molded into acrylic blocks, and 1-mm-thick sections were obtained from the middle third of each root. Specimens were mounted onto glass slides and scanned under a confocal laser scanning microscope. DTP depth, percentage, and area were measured using imaging software. Kruskal-Wallis and Mann-Whitney U tests were used for statistical analysis. The level of significance was set at P <.05. Results: No significant difference was found among the experimental groups in terms of both percentage and depth of DTP (P >.05). CH had a lower penetration area compared with TAP regardless of the vehicle used (P <.05). Conclusions: A low surface tension vehicle did not alter the penetration of CH and TAP.