Targeted endodontic microsurgery combines a precisely designed three-dimensional (3D)-printed surgical guide in which the osteotomy site and angulation is defined preoperatively to avoid damaging anatomically important structures. The current endodontic microsurgical procedures have been progressing in pace with technological advances as a predictable alternative to nonsurgical treatment of persistent and recurrent apical periodontitis. The 3D-printed template has been used earlier in the guided endodontic procedure (access openings). The endodontic microsurgery utilizes the surgical microscope and microsurgical instruments which help in enhanced magnification, illumination, and visualization compared to conventional endodontic surgery. Cone beam computed tomography (CBCT) plays an important role in surgical endodontics as it helps in measuring the distance between the cortical plate and the apex, position of the roots within the bone, and the proximity of vital structures can be assessed. The true size, location, and extent of the periapical lesion can also be appreciated preoperatively. In the present cases, the guide allowed the clinicians to precisely reach the targeted tissues in a faster and more accurate manner with a more conservative and less traumatic treatment procedure. A 1-year CBCT follow-up of both cases showed complete 3D healing of the surgical site.