BackgroundThird molar (M3) extraction is a common surgery in oral and maxillofacial surgery, and composite wound dressings such as hydroxybutyl chitosan (HBC) may improve postoperative sequala following M3 removal. PurposeThe study purpose was to measure and compare differences in pain, swelling, trismus, wound healing and quality of life (QOL) between the HBC and the control sides in patients undergoing M3 removal. Study design, setting and sampleThis study is a double-blind, split-mouth, randomized clinical trial. Patients who required M3 removal between June 2022 and May 2023 were included. Exclusion criteria included seafood allergies, smoking, poor oral hygiene, and systemic diseases. Predictor variableThe predictor variable was the socket treatment technique. Subjects were randomly assigned to the HBC or control (physiologic saline) side. Primary outcome variableThe primary outcome variables, including pain assessed by visual analog scale, swelling, and maximal incisional opening (MIO), were measured on the first, third, and seventh postoperative days. The secondary outcome variables included QOL and wound healing score measured on the third and seventh days after surgery. CovariatesThe covariates included age, sex and operation time. AnalysesThe Shapiro‒Wilk test was used to evaluate the normality of the data distribution. The paired t test or Wilcoxon signed-rank test was adopted. Statistical significance was set at P <0.05. ResultsThe study included 60 patients (mean age: 25.81 ± 4.91;23 (38%) males, 37(62%) females). A statistically significant difference in the level of pain (HBC: 37.58 ± 4.39 mm, control: 47.00 ± 4.33 mm, day 1, P < 0.001; 21.88 ± 3.25 mm, 35.95 ± 1.57 mm, day 3, P < 0.001), MIO (23.92 ± 1.38 mm, 18.22 ± 1.82 mm, day 1, P<0.001; 30.00 ± 1.61 mm, 23.78 ± 1.70 mm, day 3, P <0.001) and swelling (6.86 ± 0.70 mm, 7.15±0.80 mm, day 3, P=0.006) was detected after surgery. A statistically significant difference in QOL was detected (HBC: 13.70 ± 1.65, control: 18.60 ±2.14, day 3, P<0.001). ConclusionThe application of HBC hydrogels to wounds after impacted mandibular M3 extraction reduces postoperative sequalae, promotes wound healing and improves postoperative quality of life.