Importance: Pharyngocutaneous fistula formation is an unfortunate complication after salvage laryngectomy for head and neck cancer that is difficult to anticipate and related to a variety of factors, including the viability of native pharyngeal mucosa. Objective: To examine whether noninvasive angiography with indocyanine green (ICG) dye can be used to evaluate native pharyngeal vascularity to anticipate pharyngocutaneous fistula development. Design, Setting, and Participants: This cohort study included 37 patients enrolled from June 1, 2013, to June 1, 2016, and follow-up was for at least 1 month postoperatively. The study was performed at the University of Alabama at Birmingham, a tertiary care center. Included patients were those undergoing salvage total laryngectomy who were previously treated with chemoradiotherapy or radiotherapy alone. Exposures: The ICG dye was injected intraoperatively, and laser-assisted vascular imaging was used to evaluate the native pharyngeal mucosa after the ablative procedure. The center of the native pharyngeal mucosa was used as the reference to compare with the peripheral mucosa, and the lowest mean ICG dye percentage of mucosal perfusion was recorded for each patient. Main Outcomes and Measures: The primary outcome was the formation of a postoperative fistula, which was assessed by clinical and radiographic assessment to test the hypothesis formulated before data collection. Results: A total of 37 patients were included (mean [SD] age, 62.3 [8.5] years; 32 [87%] male and 5 [14%] female); 20 had a history of chemoradiotherapy, and 17 had history of radiotherapy alone. Thirty-four patients (92%) had free flap reconstruction, and 3 had primary closure (8%). Ten patients (27%) developed a postoperative fistula. No significant difference was found in fistula rate between patients who underwent neck dissection and those who did not and patients previously treated with chemoradiotherapy and those treated with radiotherapy alone. A receiver operator characteristic curve was generated to determine the diagnostic performance of the lowest mean ICG dye percentage of mucosal perfusion determined by fluorescence imaging, which was found to be a threshold value of 26%. The area under the curve was 0.85 (95% CI, 0.73-0.97), which was significantly greater than the chance diagonal. The overall mean lowest ICG dye percentage of mucosal perfusion was 31.3%. The mean lowest ICG dye percentage of mucosal perfusion was 22.0% in the fistula group vs 34.9% in the nonfistula group (absolute difference, 12.9%; 95% CI, 5.1%-21.7%). Conclusions and Relevance: Patients who developed postoperative fistulas had lower mucosal perfusion as detected by ICG dye angiography when compared with patients who did not develop fistulas.