Objective To study the analgesic effect and safety of saphenous nerve block (SNB) combined with infiltration between the popliteal artery and capsule of the knee (IPACK) block in patients undergoing total knee arthroplasty (TKA), to provide a clinical reference. Methods 60 patients with unilateral TKA admitted to Deyang People’s Hospital from January 2021 to January 2022 were selected as the study objects and divided into the control group (received SNB) and the observation group (received SNB combined with IPACK block), 30 patients in each group. The perioperative indicators, numerical rating scale (NRS) scores, knee range of motion and incidence of adverse reactions between two groups of patients were compared. Results There were no significant differences in operation time and duration of anesthesia between the two groups (all P>0.05). In the observation group, the press frequency of patient-controlled intravenous analgesia (PCIA) within 48 h after surgery was lower than that in the control group, the proportion of analgesic relief was lower than that of the control group, and the time of first getting out of bed and length of hospital stay were shorter than the control group (all P<0.05). NRS scores between the two groups were different in time, group, and interaction effects, in both groups, NRS scores of postoperative 72 h were lower than postoperative 24 h and 48 h, postoperative 48 h were lower than postoperative 24 h and higher than postoperative 2 h, postoperative 24 h was higher than postoperative 2 h (all P<0.05). The knee range of motion between the two groups were different in time, group, and interaction effects, in both groups, postoperative 14 d was bigger than postoperative 1 d and 7 d, postoperative 7 d was bigger than postoperative 1 d but smaller than preoperative, postoperative 1 d was smaller than preoperative (all P<0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P>0.05). Conclusion The combination of SNB and IPACK block for TKA can improve postoperative analgesic effect, promote the recovery of knee joint mobility in patients, and have ideal security.