Lesions affecting sphenoid sinus lateral recess (SSLR) are difficult to visualize and manipulate through the transnasal routes, especially when the sinus is highly pneumatized. External approaches to this area involve extensive surgery and are associated with significant morbidity. The aims of this study are to present our experience with the endoscopic transpterygoid approach as a method for approaching lesions of the SSLR and to evaluate the outcomes of this procedure. Clinical charts of patients who had lesions in the SSLR and who were treated at our institution from September 1998 to June 2018 were retrospectively reviewed. All these patients were managed by the endoscopic endonasal transpterygoid approach. Thirty-nine patients were identified. No cerebrospinal fluid leak recurrences were observed during follow-up (range: 1-19.7 years; median: 2.3 years). Hypoesthesia (temporary, 1; persistent, 4) in the region innervated by the maxillary branch of the trigeminal nerve was detected in five (12.8%) patients, while symptoms due to the Vidian nerve damage (dry eye, 3; dry nasal mucosa, 1) were present in four (10%) patients. Although the endoscopic endonasal transpterygoid approach is an excellent corridor for dealing with lesions of the SSLR, limited rate of neurologic and lacrimal complications was observed. Potential morbidity of the intervention should be discussed during preoperative counselling.© Thieme Medical Publishers.