Background Although enhanced recovery after surgery (ERAS) protocols have been widely applied during perioperative periods for different diseases, there are few reports of ERAS in patients undergoing endoscopic sinus surgery (ESS). This study therefore aimed to evaluate the benefits of ERAS protocol compared to traditional care following ESS. Methods A total of 55 patients with chronic rhinosinusitis undergoing ESS were prospectively assigned to 1 of 5 treatment groups; ERAS groups with postoperative intravenous Flubiprofen Axetil or analgesia pump, traditional care with Flubiprofen Axetil or analgesia pump (NERAS groups), or traditional care without postoperative intravenous analgesia group (control). All patients completed the Kolcaba General Comfort Questionnaire, Medical Outcomes Study Sleep Scale, and Self-rating Anxiety Scale at admission and before discharge. Pain scores were recorded at 2, 6, 24, and 48 hours postsurgery and adverse reactions to analgesics were noted. Results Patients in ERAS group demonstrated significantly higher general comfort scores and lower self-rating anxiety scores compared to patients in NERAS and control groups. Compared to control patients, patients in ERAS group reported significantly lower pain scores at 6, 24, and 48 hours. Moreover, pain alleviated from 6 hours postsurgery in ERAS group compared to 48 hours in NERAS group. Patients using opioids experienced more adverse nausea events than patients using only nonsteroidal anti-inflammatory drugs (NSAIDs). Conclusions The use of patient-tailored ERAS programs following ESS may help to attain higher general comfort and to alleviate perioperative anxiety compared with traditional perioperative care. Adequate postoperative analgesia with NSAIDs in ERAS protocol may alleviate pain earlier with fewer adverse reactions.