The purpose of this study was to examine the impact of surgical pathology, anesthesiologist experience, and airway technique on surgically relevant outcomes in patients identified by preoperative laryngoscopy to have a difficult airway due to head and neck pathology. We prospectively recorded a series of 152 difficult airway cases due to head and neck pathology out of 2,145 direct laryngoscopies undertaken between November 2005 and June 2008. One of two senior anesthesiologists specializing in head and neck procedures intubated 101 (66.4%) of the 152 patients and did so 3.3 minutes faster (p = 0.51), with better oxygenation (87.3 vs. 81.8%; p = 0.02) and fewer airway plan changes (p = 0.001) than did other, nonspecialist anesthesiologists. Predictors of failure of the first intubation plan included: cancer diagnosis (p = 0.02), previous radiotherapy (p = 0.03), and supraglottic lesions (p = 0.03). Glottic/subglottic lesions required the most intubation attempts (p = 0.02). Awake fiberoptic intubation was the most common method used (44.7%) but resulted in a change in the airway plan in 6 cases (8.8%). Gas induction maintained the best oxygenation (p = 0.01). Awake tracheostomy was infrequent (1.3%) and took the longest (p = 0.006). We concluded that difficult airways due to head and neck pathology require teamwork and a backup plan. An anesthesiologist specializing in head and neck procedures may help to avoid adverse outcomes associated with cancer, especially previously irradiated supraglottic/glottic lesions, leading to a less frequent need for awake tracheostomy.