Teeth having open apices in the absence of a natural apical constriction pose several challenges during conventional endodontic treatment, especially when establishing an apical seal. Treatment is further challenging when these teeth are associated with large periapical or cystic lesions having resulted in expansion and/or thinning of adjacent cortical plates. Although surgical intervention is commonly adopted in the management of such cases, a conservative treatment option offering equally good prognosis is always desirable. This case series describes 3 cases: a 39-year-old woman, a 45-year-old woman, and a 15-year-old boy having teeth with concomitant open apices and large periapical/cystic lesions managed conservatively by (1) following a strict intracanal disinfection protocol, (2) intracanal aspiration with digital decompression of associated swelling, and (3) 1-step apexification for closure of the root apex by placing a preliminary barrier of platelet-rich fibrin (PRF) and a secondary barrier of Biodentine (Septodont, Saint-Maur-des-Fossés, France). In all 3 cases, the treatment outcomes, both clinical and radiographic, were highly satisfactory. PRF and Biodentine collectively rendered an apical plug that proved to be a suitable alternative to commonly used mineral trioxide aggregate in 1-step apexification. Biodentine provides good interfacial adhesion and sealing with dentin attributed to its property of hydroxyapatite crystal deposition at the material-dentin interface. Also, because of its bioactivity, it likely promotes the conversion of adjacent PRF into a calcific barrier, thus reinforcing the apical seal. Additionally, host-modulating responses of PRF contribute in expediting the healing process. Reasonable osseous healing in the periapex could be appreciated as early as 3 months in all patients. The rapidity with which healing occurred may have been an incidental finding but definitely draws attention.