Context: This study focuses on the marginal adaptation of a calcium silicate-based cement to the root dentin after retrieval of different intracanal medicaments. Aim: This study compared the marginal adaptation of a calcium silicate-based cement to radicular dentin in the apical third of the root canal following the use of three different intracanal medicaments. Materials and Methods: Forty single-rooted premolar teeth ( n = 40) were decoronated 13 mm above the root apices; then, 3 mm of the root tips were resected to standardize the root length. Orthograde cleaning and shaping were done using the rotary files and apical enlargement using peeso reamers. Depending on the intracanal medicament used, the samples were equally divided into four groups: Group 1 - control, Group 2 - Metapex, Group 3 - triple antibiotic paste (TAP), and Group 4 - calcium hydroxide with Propolis. Subsequently, the medicament was removed and a 3 mm apical barrier of Biodentine TM was placed and later scanned using an ex vivo micro-computed tomography scanner. Statistical Analysis Used: One-way ANOVA F -test and Tukey's post hoc test were used. Results: Maximum adaptation was seen in control group (0.65) > Propolis (1.47) > TAP (4.37) > Metapex (5.25); a high statistically significant difference between the four groups was found ( P < 0.001) with regard to the external voids between Biodentine TM and radicular dentin. Conclusion: On comparison of the marginal adaptation of Biodentine to root canal dentin following the use of three different intracanal medicaments, maximum adaptation was seen in Group 1, followed by Group 4, Group 3, and Group 2.