Background Sphenopalatine artery (SPA) ligation or cauterization stands to be one of the most common management options of refractory epistaxis. Ramification pattern of SPA as it passes through sphenopalatine foramen (SPF) has not been clearly established. The aim of this study is to investigate situations in which middle meatal approach may fail due to anatomic variations of SPA and to define a minimally invasive surgical cauterization procedure. Anatomic variations of SPA were determined by microdissection of 20 adult sagittally cross-sectioned head specimens. Methods Branching characteristics of SPA and its anatomic relations were evaluated and anatomic variations were noted. Results SPA was generally (80%) forming branches within SPF before entering into the nasal cavity. In 20% of the specimens, SPF was located superior to the horizontal lamella of the middle turbinate, and accessory foramen was present in 10%. In 10% of the cases, the posterior lateral nasal branch was situated as two branches in a deep sulcus in the middle meatus. Conclusion The ramification pattern of SPA can not be fully exposed without resection of the posterior part of the middle turbinate via the middle meatal approach. Two-step procedures are advocated in reducing failure rates. Previously defined two-step procedures are relatively invasive. A less invasive procedure is defined based on the variations of SPA and SPF.