Guided apicoectomy performed with 3D-printed polymer-based static surgical guides is an emerging trend in endodontic surgery. Static-guided apicoectomy is carried out with either a drill or a trephine. The aim of this in vitro study was to assess the accuracy of osteotomy and apicoectomy performed through a polymer guide, with both drill and trephine, and to compare the accuracy achievable with the two instruments. Six plaster models of a maxilla master model with extracted human maxillary teeth in polymethyl-methacrylate resin were used. The modeled osteotomies were performed in these. The master model was CBCT-scanned, and digital surgical plans were prepared, based on which the surgical guides were printed. The plans contained both drill and trephine apicoectomies. Digital three-dimensional position analysis was performed with dedicated algorithms. A total of 39 drill and 47 trephine osteotomies were analyzed. A statistically significant difference between the two instruments was found only in the global deviation of the distal endpoint, indicating lower deviation for the trephine procedure (1.53 mm vs. 1.31 mm, p = 0.038). Nevertheless, from a clinical perspective, this distinction is inconsequential. The results suggest that, for all practical purposes, the two approaches to apicoectomy allow the same level of accuracy.