Pharyngocutaneous fistula after laryngectomy is common and significantly increases the morbidity of the procedure. Intraoperative, objective variables that can reliably predict fistula formation would be useful to surgeons deciding how to reconstruct the laryngectomy defect. Retrospective chart review of 50 radiated patients and 10 non-radiated patients who underwent total laryngectomy at a single tertiary care institution. Patients with pharyngocutaneous fistula were selected to ensure a representative sample were available for comparison. All patients had pathology slides available for re-review by a single, blinded pathologist. Margins of both radiated (n = 50) and non-radiated (n = 10) larynges were examined for 7 histologic features, and odds ratios were calculated to assess whether these features were associated with fistula. When evaluating all 60 patients, both telangiectatic capillaries and hyalinized arterioles were associated with fistula (OR 3.72 and 9.21, respectively). Collinearity between the variables was evaluated; findings indicated a high likelihood of having hyalinized arterioles if telangiectatic capillaries were also present (OR 31.67 [3.13, 320.06]). Microvascular changes in radiated tissue have previously been described in other anatomic subsites, but the larynx and pharynx have not been specifically evaluated. Laryngectomy mucosal margins appear to display similar changes, and evidence of this damage may be associated with fistula formation. These features could potentially guide the surgeon to alter the reconstructive technique.