Objective: Study the roll of periarticular anesthetic regimen on postoperative pain, rehabilitation, and length of Hospital stay after Total knee Arthroplasty. Method: This is a non-Randomised Prospective study carried out at Ark hospital, Andheri Mumbai, from Jan 2016 to May 2017. This is a comparative study between two group. Group 1 have 26 patients (21female, 5 male) and Group 2 have 25 patients (20 female, 5 male) from this hospital. Group 1 (study group): -comprises of patients who had received a Periarticular infiltration with following combination before wound closure. Inj. Bupivacaine (0.5%) + Inj. cefuroxime 1.5gm + Inj. Buprenorphine (0.3mg/ml). Group 2 (control group):-comprises of patients who had received a Periarticular infiltration same as above but, without Buprenorphine and Bupivacaine before wound closure. All patients were operated by same technique by medial parapatellar incision. Result: The majority of the patient were from the age group of 61-78 yr in both groups. There was no significant difference between two groups in terms of gender wise distribution. There were no significant differences among 2 groups for Nausea, vomiting, constipation, sedation, diabetes, hypertension and ischemic heart disease. Hypertension was present in maximum number of patients.. In group 1 patients were more actively participate in rehabilitation programme and obtain higher patient satisfaction as compare to group 2. The average hospital stay in group 1 was 4.06 days and in group 2 was 5 days. Conclusion: Periarticular infiltration technique with multimodal drugs after TKA can significantly improve pain control both during rest and on movement and hence patient more actively participate in rehabilitation programme and obtain higher patient satisfaction. It can significantly reduce the opioid related side effect, early discharge from the hospital and therefore is cost effective.