Background: Pain, edema, and trismus are predictable sequelae for surgical extraction of impacted mandibular third molars (M3M). The present study aimed to compare the anti-phlogistic potential of bromelain and aceclofenac in the reduction of post-surgical sequalae in the extraction of impacted M3M.Method: A randomized controlled, triple-blinded clinical study included 72 patients scheduled for surgical removal of impacted M3M under local anesthesia. Randomization was performed and subjects were equally allocated to groups A (control) and B (study), who intended to receive aceclofenac and bromelain, respectively. The primary outcome variables were pain, edema, and trismus evaluated on postoperative days 2 and 7 and compared with baseline values. The secondary variables evaluated were the quantity of rescue analgesics required and the frequency of adverse effects in both groups for 7 postoperative (PO) days. Data were analyzed with a level of significance of P < 0.05. Results: Group B demonstrated a significant decrease in the severity of edema and trismus compared to group A on both PO days 2 and 7 (P < 0.001). Bromelain demonstrated similar analgesic efficacy with an insignificant difference compared to aceclofenac (P > 0.05). Conclusion The present study showed that the efficacy of bromelain was comparable to that of aceclofenac in reducing inflammatory complications following surgical removal of impacted M3M. Bromelain can be considered a safe and potent alternative to routinely used aceclofenac when addressing inflammatory outcomes after surgery.