Objective To explore the application of enhanced recovery after surgery (ERAS) in pain management after knee arthroplasty (TKA). Methods Doctor-nurse pain management team was established based on ERAS between June and July 2016, and the pain management was carried out after training the doctors and nurses. According to the formula of two-sample mean comparison and inclusion and exclusion criteria, 60 TKA patients admitted to the hospital from March to May 2016 were assigned into the control group (before intervention) and 60 TKA patients admitted from August to October 2016 were assigned into the trial group (after intervention). The patients in the control group received routine pain management. In the trial group, preventive analgesia was performed, pain health education paths were built and ISBAR communication mode was made preoperatively; anesthesia protocols were optimized intraoperatively; multimodal analgesia based on time-demand was used postoperatively; continuing analgesia program was provided at the discharge. The pain score, Hospital for Special Surgery (HSS) knee score, average length of stay (ALOS) and average hospitalization cost (excluding materials) were compared between the two groups. Results The pain scores between the two groups at the admission and 6 hours after surgery were not statistically different (P>0.05), and the pain scores in the trial group 24, 48, 72 hours after surgery were significantly lower than those in the control group (P<0.05). The HSS scores between the two groups at the admission were not statistically different (P>0.05), and the HSS scores in the trial group 3 days, 1 week, and 1 month after surgery were significantly higher than those in the control group (P<0.05). And ALOS and average hospitalization cost (excluding materials) in the trial group were significantly lower than those in the control group (P<0.05). Conclusion The application of ERAS in pain management after TKA can effectively alleviate the postoperative pain, improve the patients’ knee function, shorten the ALOS, and decrease the average hospitalization cost.