Various surgical approaches to the infratemporal fossa (ITF) have been reported. Among them, the preauricular transzygomatic anterior ITF approach (anterior ITF approach) has been used for exposure of the antero-superior part of the ITF. The purpose of this article is to show anatomical dissections using the anterior ITF approach and to evaluate our surgical experience using this approach. An anatomical study of the anterior ITF approach was performed using six sides of three cadaveric heads. Clinical course was retrospectively reviewed for 34 patients who underwent microsurgical resection of tumor in or around the ITF using this approach. Medical, surgical, and neuroimaging records of these patients were evaluated. The key point of this approach was mobilization of the second and third divisions of the trigeminal nerve after drilling of the lateral loop between the foramina rotundum and ovale. After mobilization of the trigeminal nerve, the auditory tube, tensor veli palatini muscle, and pharyngobasilar membrane could be seen. Removal of the pterygoid muscles and plates allowed surgical access to the ITF, orbit, maxillary sinus, pterygopalatine fossa, and parapharyngeal space. We used this approach in 31 patients with skull base tumors between 1994 and 2007. Gross total removal was achieved in 27 of the 31 patients. No mortality or severe morbidity was encountered. Therefore, the anterior ITF approach provides easy access to the ITF and adjacent regions without destruction of important organs.