Aims: To evaluate whether a combination of locally administered morphine (1 mg) and lidocaine as part of a multimodal analgesic approach is safe, and whether it improves pain control during the first 24 hours after odontogenic maxillary cyst removal under general anesthesia compared to local lidocaine alone. Methods: In a double-blind, sham-controlled, single-center trial, patients scheduled for surgical removal of an odontogenic maxillary cyst under general anesthesia were randomly assigned to receive a local injection of lidocaine solution with either 1 mg of morphine (MLA group) or with no morphine (LA group). Pain management included intravenous acetaminophen (1 g every 6 hours) in all patients. Upon request, the patients could additionally receive ketoprofen (first-line additional analgesia) or tramadol (second-line additional analgesia). Pain intensity was assessed using a numeric rating scale. Primary outcome measures were (1) no need for any additional analgesic therapy and (2) time to the first rescue analgesic therapy during the first 24 hours after the surgery. Results: Of 48 eligible patients, 24 were allocated to the MLA group and 24 to the LA group. The necessity of additional ketoprofen therapy did not differ significantly between the groups (25.0% vs 50.0%, P = .074). According to the Kaplan-Meier analysis, the probability of remaining without additional analgesic intervention was significantly higher in the MLA group (log-rank test, P = .040), but there were no significant (P > .05) differences in overall and maximum pain severity between the two groups. No adverse effects of morphine were recorded. Conclusion: Within the limitations of this study, local administration of 1 mg of morphine prior to the surgical removal of an odontogenic maxillary cyst was safe, but it did not prove to be very effective as an add-on therapy for postoperative pain control. Keywords: inflammatory pain, odontogenic cysts, opioid receptors, oral surgery, peripheral opioid analgesia