Abstract: Objective To study the clinical effects and safety of different applications of cocktail treatment in total knee replacement under enhanced recovery after surgery(ERAS) mode. Methods Total 120 cases of total knee replacement during June 2016 to June 2018 in the Department of Joint Surgery of the Affiliated Suzhou Hospital of Nanjing Medical University were included. Patients were randomly divided into three groups:group A(total complex liquids of cocktail were infused and injected to the surroundings of the knees), group B(the cocktail was injected to the knee cavities), and group C(one part of the complex liquids of cocktail was infused and injected to the surroundings of knees, and the other part was injected to the knee cavities). Age, gender, BMI and other related indicators were observed and compared. Results In 6 hours, 8 hours, 12 hours, 24 hours postoperative VAS assessment, group B had the highest score and group C had the lowest score, the difference had statistical significance(all P<0.05). In 48 hours, 72 hours postoperative VAS assessment, the difference had no statistical significance(all P>0.05). In postoperative relief analgesic rate during 24 hours, group B had the highest score and group C had the lowest score(P<0.05). In the postoperative maximal decreased value of hemoglobin, group C had the lowest score and group B had the highest score(P<0.05). In the volume of drainage during 24 hours after surgery, group C had the lowest volume, group B had the highest volume(P<0.05). The patients in group C could have functional exercise in a larger scale(P<0.05). Compared with the other two groups, group C had a higher 3 days postoperative HSS assessment(P<0.05). There was no significant difference in the other indicators(all P>0.05). Conclusion The method of local infiltration combined with intraarticular injection of cocktail compound liquid in total knee arthroplasty under ERAS mode can effectively reduce patients' pain and blood loss after operation, which is safe and beneficial to patients' postoperative recovery.