The purpose of the present study was to clinically and radiographically evaluate the periapical healing responses of patients with persistent apical periodontitis who were treated with microsurgical techniques and root-end fillings with mineral trioxide aggregate (MTA). Ninety-seven consecutive patients with 128 teeth demonstrating persistent periapical lesions were included in the study. A modern endodontic surgical protocol, which included mucoperiosteal flap elevation, an ostectomy, root-end resection, ultrasonic root-end preparation, and root-end filling with MTA, was performed. One year later, all of the patients were examined clinically and radiographically. Chi-square tests were used to analyze the results. The radiological and clinical evaluations indicated success in 57.7% of the patients, improvement in 35.1%, and failure in 7.2%. No statistically significant differences were found in the treatment results according to sex, age, or tooth type. A statistically significant relationship (P<0.05) was noted between the size and type of lesion and prognosis. The larger lesions and cysts had the worst prognoses. The use of state-of-the-art microscopes, microinstruments, and ultrasonic tips and more biologically acceptable root-end filling materials in strict microsurgical approaches produces better outcomes in patients with persistent apical periodontitis.