Abstract: Objective To explore the effects of 3D printing patient-specific instruments (PSI) on lower limb force line and perioperative blood loss in patients with total knee arthroplasty (TKA). Methods Clinical data of 100 patients who received TKA from January 2019 to December 2021 were retrospectively analyzed. According to the outcome of preoperative doctor-patient communication, 47 patients received PSI-TKA (PSI-TKA group) and 53 patients received traditional TKA (the traditional group). Perioperative blood loss and lower limb force line were compared between the two groups. Results The operative time in PSI-TKA group was significantly longer than that in the traditional group, and the dominant blood loss was significantly lower than that in the traditional group (all P < 0.05); There were no significant differences in complications, total blood loss and recessive blood loss between the two groups (P > 0.05). Joint fluid transforming growth factor-β1 (TGF-β1) level, hospital for special surgery (HSS) and range of motion (ROM) of knee joint significantly increased in both groups 3 months after surgery and at the last follow-up (P < 0.05); Joint fluid tumor necrosis factor-α (TNF-α) level and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score significantly decreased (P < 0.05), but there was no significant difference between the two groups (P > 0.05). The coronal hip-knee-ankle (HKA) angle deviation in PSI-TKA group was significantly lower than that in the traditional group at the last follow-up before discharge (P < 0.05), but the incidence of force line deviation before discharge was not significantly different between the two groups (P > 0.05). Conclusion 3D printing patient-specific instrument for TKA can achieve similar effects as traditional TKA, both of which can reduce the level of inflammatory factors in the joint fluid, promote the functional recovery of the knee joint and increase the range of motion. Although the former has a relatively long operation time, it has obvious advantages in restoring the coronal position of the lower limb force line and reducing the dominant blood loss. [Key words] Total knee arthroplasty; 3D printing patient-specific instrument; Lower limb force line; Perioperative blood loss