AimThis study aimed to investigate 2‐year changes in periapical trabecular patterns in single‐rooted teeth with apical periodontitis using fractal analysis and periapical index (PAI) after root canal treatment performed with or without BioPure MTAD solution.MethodologyIn this randomized clinical trial, 100 patients were selected and randomized to either the BioPure MTAD or the control groups. Initial periapical radiographs were obtained for each participant before and 2 years after root canal treatment. The region of interest in the periapical lesion around the root apex was selected from the paired periapical radiographs, and then, the fractal dimension (FD) was calculated. With regards to the classification of periapical status, PAI was labelled as “healed” (PAI ≤ 2) or “unhealed” (PAI ≥ 3).ResultsAfter 24 months, 28 patients did not comply with the follow‐up and the data of 72 patients were compared. When the initial and the follow‐up PAI scores were compared, the decrease was statistically significant in 33 of 37 teeth (89.2%) and 32 of 35 teeth (91.4%) in the BioPure MTAD and control group, respectively. In both groups, statistically significant increases were observed in FD values after 2 years in all patients (p < .001). No significant difference was found between the two groups amongst decreased PAI scores and increased FD values.ConclusionsRoot canal treatments with or without BioPure MTAD irrigation contributed to periapical healing in single‐visit root canal treatment. Two years after root canal treatment, the extent of the periapical trabecular bone radiographically increased, as the FD and PAI data revealed.