To evaluate the efficacy of image-guided surgical navigation (IGSN) in otologic surgery and establish practice guidelines. Prospective study. Between January 2003 and January 2010, all patients requiring complicated surgery for chronic otitis media, glomus jugulare, atresia, cerebrospinal fluid leak with or without encephalocele, and cholesterol granuloma of the petrous apex were offered IGSN. The accuracy of IGSN relative to pertinent pathology and 11 anatomic landmarks was established. Additionally IGSN-related operative time, complications, and surgical outcome were recorded. In the study period there were 820 otologic procedures, among 94 patients (96 ears) with disease meeting proposed criteria. Thirteen patients (15 procedures) consented to the use of IGSN. All patients had a minimum 6 months of follow-up. The average additional operative time required was 36.7 minutes. The mean accuracy error was 1.1 mm laterally at the tragus but decreased to 0.8 mm medially at the level of the oval window. The mean accuracy of IGSN was within 1 mm in 10 of the 11 targeted surgical anatomic landmarks. Interactive image-guided surgical navigation during complex otologic surgery may improve surgical outcome and decrease morbidity by providing an accurate real-time display of surgical instrumentation relative to patient anatomy and pathology. In select cases, the extra cost of imaging immediately prior to surgery and extra operating room time may be compensated by enhancing the ability to distinguish distorted anatomy relative to disease, potentially improving surgical outcome. IGSN, although useful, does not replace surgical expertise and experience.