the preemptive analgesic efficacy and adverse effects of preoperatively administered piroxicam-β-cyclodextrin for post-endoscopic sinus surgery pain was determined in a prospective, double-blind, randomized, clinical study. seventy-five american society of anesthesiologists status i-ii patients, aged 18-65 years, were divided into three groups with similar demographic characteristics: group 1 received 20 mg piroxicam-β-cyclodextrin, group 2 received 40 mg piroxicam-β-cyclodextrin and group 3 received placebo orally before induction of general anesthesia. a blinded observer recorded the incidence and severity of pain at admission to the post-anesthesia care unit (pacu), at 15, 30, and 45 min in the pacu, and 1, 2, 4, 6, and 24 h postoperatively. all patients received patient-controlled morphine analgesia during the postoperative period and consumption was recorded for 24 h. during the pacu period, mean visual analogue scale values were significantly lower in groups 1 and 2 compared to group 3 (p < 0.05). during the postoperative period, morphine consumption was 3.03 ± 2.54, 2.7 ± 2.8, and 5.56 ± 3.12 mg for each group, respectively (p < 0.05). as a side effect, bleeding was observed in groups 1 and 3, nausea and vomiting in all groups, and edema only in group 3. however, no significant differences were detected in any of the parameters analyzed, which also included epigastric pain, constipation/diarrhea and headache. similar hematological test results were obtained for all groups. preemptive administration of piroxicam-β-cyclodextrin effectively reduced analgesic consumption, and 40 mg of the drug was more effective than 20 mg piroxicam-β-cyclodextrin without side effects during the postoperative period.