We have performed a detailed morphometric analysis of the length and anatomic routes of the greater palatine canal (GPC) and a systematic review of the literature on the anatomy of the GPC with the aim of informing dentists, maxillofacial surgeons, otorhinolaryngologists and other specialists performing procedures in the area of the GPC. In total, we analysed 1,500 archived adult head computed tomography scans to determine the length of the GPC and of the routes on both sides, as well as the dimensions and opening directions of the greater palatine foramen. The systematic review of the literature was performed according to PRISMA guidelines. The study group comprised 783 females (52.2 %) and 717 males with a mean (± standard deviation) age of 42.1 ± 16.9 years; there was significant difference in age between sexes (p = 0.33). The average length of the GPC was 31.1 ± 2.9 (range 15–44) mm. The GPC travelled three different paths in the sagittal plane and four different paths in the coronal plane. Most often it descended from the pterygopalatine fossa inferiorly before changing to an anterior-inferior direction (68.4 %; sagittal plane) and inferior-laterally before changing to an inferior-medial direction (40.7 %; (coronal plane). In total, the GPF had four different opening directions: inferior-anterior-medial (82.1 %), inferior-anterior-lateral (4.0 %), anterior (7.6 %), and vertical (5.3 %). Twenty-five studies were included in the systematic review. In conclusion, the information presented here provides clinicians with the anatomical knowledge necessary to minimize the risk of complications when performing procedures involving infiltration of the GPC.