Background: The sphenopalatine ganglion block (SPGB) with local anesthetic is used to treat facial pain and headache of various etiologies; it has been widely used during functional endoscopic sinus surgery (FESS). The purpose of this study was to investigate whether preemptive SPGB may positively impact postoperative pain and functional outcomes after FESS. Methods: A prospective, double-blind, randomized, placebo-controlled study was performed. A total of 60 patients (18-70 years), undergoing general anesthesia for bilateral FESS, were randomly assigned to receive SPGB with either 2 mL 0.25% bupivacaine with epinephrine 1:100,000 (BP, treatment group) or normal saline (NS, control group). SPGB was performed preemptively 10 minutes before the start of surgery. Preoperative and postoperative (day 0, day 7, and day 30) visual analog pain scale, Sino-Nasal Outcome Test (SNOT-20), computed tomography (CT) and endoscopic scores were compared between the 2 groups. Results: A total of 29 patients were enrolled in BP, and 27 were enrolled in NS. Three patients withdrew from the study, and 1 was withdrawn by the investigator due to severe hypertension after induction of anesthesia. There were no differences in patient demographic characteristics between the study groups. On day 7, the mean visual analog pain scales were 1.12 ± 0.3 in NS and 0.48 ± 0.23 in BP (p = 0.053). There were no statistical differences in other outcome measures (SNOT-20, CT and endoscopic scores) between the 2 groups. Conclusion: A limited trend toward reduced postoperative pain after FESS was noted with bupivacaine compared to saline, but statistical significance was not achieved. Preemptive SPGB may offer sinonasal symptomatic benefits for patients undergoing FESS, but larger studies are warranted. © 2011 ARS-AAOA, LLC.