To assess the predictive value of wound amylase as an indicator for pharyngocutaneous fistula development following laryngectomy for cancer.We conducted a prospective observational study at a tertiary referral center of 102 consecutive laryngeal or hypopharyngeal cancer patients undergoing laryngectomy with or without pharyngectomy.Data were collated on potential predictors of fistula formation compared with rate of development of clinical fistulas, all confirmed radiologically.Rate of fistula formation was determined for the following potential predictors: extent of resection (extended laryngectomy), postoperative wound (drain) amylase, previous radiotherapy, neck dissection, preoperative and postoperative hemoglobin and albumin levels, and postoperative transfusion. Sensitivity, specificity, and positive and negative predictive values of significant predictors were ascertained.The only significant predictors of fistula formation were extent of resection (extended laryngectomy) and drain amylase >4000 IU/L. If both factors are combined, the sensitivity, specificity, and positive and negative predictive values for fistula development are 83, 94, 63, and 98 percent, respectively.We advocate that patients be managed postoperatively according to the presence or absence of these given predictors to reduce occurrence of fistula formation in the high-risk group.