Apical periodontitis is a prevalent inflammatory condition affecting the tissues surrounding the root apex of a tooth. The selection of appropriate intracanal medicaments for its management remains a topic of ongoing research. This study aimed to investigate the effect of calcium hydroxide and triple antibiotic paste on the healing of apical periodontitis.A total of 304 teeth from 215 patients with apical periodontitis were included in this observational study. Patients were randomly assigned to three groups: Group A (calcium hydroxide), Group B (triple antibiotic paste), and Group C (control). Baseline characteristics were recorded, and follow-up assessments were conducted at three, six, and 12 months. Parameters such as reduction in apical radiolucency, presence of periapical healing, bleeding on probing (BOP) percentage, clinical attachment level (CAL), and periodontal depth were evaluated.At baseline, the three groups exhibited similar distributions of apical periodontitis parameters. Over the 12-month follow-up, Group A and Group B demonstrated a significant reduction in apical radiolucency compared to Group C (p < 0.05). The presence of periapical healing was more frequent in Group A (85%) and Group B (80%) compared to Group C (60%). Group A showed the lowest mean BOP percentage (15.2 ± 3.5), followed by Group B (18.6 ± 4.2) and Group C (22.1 ± 4.8). Similarly, Group A demonstrated the highest mean CAL (5.8 ± 0.9 mm) and the lowest mean periodontal depth (3.2 ± 0.6 mm). Group B exhibited intermediate values for CAL (5.2 ± 1.1 mm) and periodontal depth (3.6 ± 0.8 mm).In this study, both calcium hydroxide and triple antibiotic paste demonstrated potential therapeutic effects in promoting healing and reducing apical radiolucency compared to the control group. Calcium hydroxide exhibited the most favorable outcomes, with a higher presence of periapical healing, lower BOP percentage, and superior CAL and periodontal depth measurements. These findings contribute to the understanding of intracanal medicaments' effectiveness in apical periodontitis management.