Objective To study the analgesic effect of a new “cocktail” of local infiltration analgesia (LIA) with Deprosone after total hip arthroplasty (THA). Methods In a prospective randomized controlled study, 100 patients with hip joint disease requiring unilateral primary THA in West China Hospital of Sichuan University between January 2018 and December 2018 were enrolled and randomly divided into observation group and control group, with 50 cases in each group. There was no significant difference in age, gender, operative side, disease type, body mass index, American Society of Anesthesiologists (ASA) classification, preoperative rest and activity visual analogue scale (VAS) score, hip Harris score (HHS), quality of life scale (SF-12) score, and other general data between the two groups (P>0.05). The patients in the observation group were treated with a new “cocktail” LIA around the hip joint before suturing the incision, and the drug formula was ropivacaine 200 mg, Diprospan 1 mL, morphine 10 mg, and added normal saline to 80 mL; the patients in the control group were not treated with LIA. The operation time, postoperative hospital stay, the amount of morphine used during hospitalization, and the range of motion of hip joint at discharge were recorded, and the complications were counted. The VAS score at rest and activity, HHS score, and SF-12 score [physiological score (PCS) and psychological score (MCS)] of the hip joint were recorded before and after operation, and the postoperative analgesic effect and the recovery of hip joint function were evaluated. Results There was no significant difference in the operation time between the two groups (P>0.05), and the postoperative hospital stay in the observation group was significantly shorter than that in the control group (P<0.05). The postoperative morphine consumption in the observation group was significantly less than that in the control group (P<0.05), and the total morphine consumption in the observation group was less than that in the control group during hospitalization, but the difference was not significant (P>0.05). Patients in both groups were followed up to 6 months after operation. The resting VAS scores of the observation group were significantly lower than those of the control group at 2, 6, 12 hours after operation and in the morning and afternoon of the first day after operation, and the active VAS scores of the observation group were significantly lower than those of the control group at 6, 12 hours after operation and in the morning of the first day after operation, and the differences were significant (P<0.05). There was no significant difference in the resting and active VAS scores between the two groups on the day of discharge and at 3 and 6 months after operation (P>0.05). At discharge, the flexion range of motion of hip joint in the observation group was significantly greater than that in the control group (P<0.05), but there was no significant difference in the abduction range of motion of hip joint between the two groups (P>0.05). There was no significant difference in HHS score and SF-12 score between the two groups at 3 and 6 months after operation (P>0.05). There was no significant difference in analgesic satisfaction and functional satisfaction between the two groups at last follow-up (P>0.05). There was no complication such as skin pruritus, superficial and deep infection of incision, skin necrosis, deep venous thrombosis of lower extremity, and pulmonary embolism in both groups. There was no significant difference in the incidence of complications such as nausea and vomiting, urine retention, fat liquefaction of incision, local hematoma, and large fluctuation of blood sugar between the two groups (P>0.05). ConclusionThe new “cocktail” LIA with Diprospan can effectively reduce the early postoperative pain of THA, reduce the dosage of opioids, shorten the length of hospital stay, and is conducive to the early functional rehabilitation of patients.