To explore the correlation between detection results of pepsin in vocal fold polyp tissues and the postoperative efficacy.The clinical data of 112 patients with vocal fold polyp who received surgical procedures in our hospital from June 2019 to March 2021 were retrospectively analyzed. The vocal fold morphology and vocal acoustic function were assessed at postoperative week 12. Using binary logistic regression, we explored whether the factors, ie, detection result of pepsin in vocal fold polyp tissue, microscopic suturing, the use of CO2 laser, and the history of smoking, affected the postoperative morphological repair of vocal fold polyps. Then, to observe and compare the influence of the detection results of pepsin on the recovery of vocal acoustic function, we divided the enrolled patients into the pepsin group and the pepsin-free group based on the postoperative detection results of pepsin in the polyp tissues by immunohistochemistry, RESULTS: In the 112 patients with vocal fold polyps, positive staining of pepsin in the postoperative samples was found in 76 patients (67.86%) and negative in 36 (32.14%). Totally 80 patients returned to normal in vocal fold morphology, among whom 32 (88.89%) were in pepsin-free group and 48 (63.16%) in pepsin group. Binary logistic regression showed that pepsin was a clinically significant indicator that affected the postoperative morphological recovery of the vocal fold (P = 0.003). Although hoarse voice was improved in all patients at postoperative week 12, the differences were statistically significant in the proportion of patients with grade, roughness, breathiness, asthenia, strain class G, voice handicap index, maximum phonation time, Jitter, Shimmer and noise-to-harmonic ratio between the pepsin group and the pepsin-free group (P < 0.05), with the pepsin-free group being superior to the pepsin group in the improvement of vocal acoustic function.Pepsin in vocal fold polyps is a clinically significant indicator affecting the postoperative morphological recovery and acoustic efficacy, and patients with negative pepsin are superior to those with positive pepsin in the postoperative recovery of vocal fold morphology and function.Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.