Introduction:Ideal chemo-mechanical preparation with good obturation produces a monoblock and three-dimension hermetic root canal seal. The importance of sealing is the prevention of leakage, reinfection, periapical lesion, and the root fracture. Aim: The purpose of this in vitro study was to evaluate and compare the effect of different irrigating solutions on the apical sealing ability of two sealers (Bioceramic and Resin based sealers). Materials &Methods: One hundred fifty-five extracted human single-rooted mandibular premolars were prepared and classified into three main groups depending on their final irrigation regimens; group A: 17% Ethylene-diamine tetraacetic acid (EDTA), group B: 10% citric, and group C: 16 ppm ozonated water. Each group was subdivided into two subgroups based on the type of sealer applied, subgroup1: TotalFill ® BC Sealer and subgroup 2: AH Plus ® sealer. Each subgroup was then divided into two divisions based on the time of evaluation, T1: immediately after incubation and T2: after 30 days. The Apical Sealing Ability was measured for all samples using fluid infiltration method. Statistical analysis was performed using ANOVA (one-way and three-way) and t-test (paired and unpaired). Statistical significance was considered at P<0.05. Results: In relation to irrigation, the highest apical microleakage mean values were recorded in group B, and the least mean values were recorded in group A, followed by group C. In relation to sealers, the highest mean values were recorded in subgroup1, and the least mean values were recorded in subgroup2. In relation to time, the highest mean values were recorded in division 2 and the least mean values were recorded in division 1. Conclusion: AH plus sealer provided better apical sealing than Totalfill BC sealer. Sealers sealing performance is improved by 17% EDTA and 16 ppm Ozonated water. Apical sealing ability decreased over time, regardless of the irrigation and sealer types used.