Background: Removal of impacted third molars is associated with postoperative complications such as pain, swelling, ecchymosis, trismus, infection, and hematoma. Thus, contemporary surgery aims to reduce complications by applying collagen or hyaluronic acid in the socket after extracting the impacted mandibular third molars.This study aimed to study the efficacy of Hyaluronic Acid (HA) addition to collagen, compared to collagen application alone, on the magnitude of swelling and trismus following impacted mandibular third molar surgery.Methods: About 20 patients underwent impacted bilateral lower third molars surgery (n = 40). Opaque envelopes carried out randomization; two materials were applied topically in the socket collagen alone or with hyaluronic. The post-operative mouth-opening limitation and swelling rate were assessed on the third and seventh days after the extraction. Results: The mean age was 22.7 ± 3.079 years (75% female, 25% male). A statistically significant difference was detected for the trismus between the two treatment groups on the seventh (p= 0.005) but the difference between the groups was not statistically significant on the third day (p= 0.061). The swelling scores of the hyaluronic acid addition group were significantly lesser than those of the collagen alone group on the third and the seventh days (p<0.05) except for lateral canthus to angulus mandibulae on the third day (p= 0.133).Conclusion: Adding hyaluronic acid to collagen could effectively reduce the severity of facial swelling and trismus following surgical extraction of impacted lower third molars.Trial registration: The trial was registered in the Isrctn.com database (06/07/2021, ISRCTN16820104).