Background Both lumbosacral plexus block (LSPB) and local infiltration analgesia (LIA) can provide postoperative analgesia for patients undergoing total hip arthroplasty (THA). The current study aimed to compare the differences between LSPB and LIA on postoperative pain and quality of life (QoL) in THA patients. Methods A total of 117 patients aged 40–80 years, ASA I-III, were prospectively randomized into two groups: a general anesthesia plus LSPB (Group LSPB) and a general anesthesia plus LIA (Group LIA). Pain intensity and opioid consumption were recorded Within 72 hours after surgery. QoL was measured by EQ-5D and EQ-VAS questionnaires, and the incidence of postoperative pain was measured as part of the EQ-5D on day 1, day 3, day 7, and month 1, month 3, and month 6 after surgery. Results EQ-5D scores: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression were higher in Group LSPB versus Group LIA throughout six-month follow-ups (p = 0.039). The pain intensity was lower in Group LSPB than in Group LIA 0–12 h after surgery (2.41 vs 2.79, p = 0.01), but was higher in Group LSPB than in Group LIA 12–24 h (2.59 vs 2.05, p = 0.02) and 24–48 h (2.18 vs 1.73, p = 0.02) after surgery. There were no differences in opioid consumption between the groups during the first 72 postoperative hours. In the first month after surgery, more patients in Group LSPB than in Group LIA had no pain (52 vs 40, p = 0.04). Conclusion Both LSPB and LIA can provide satisfactory postoperative analgesia. The LSPB is better than LIA for long-term QoL in THA patients undergoing general anesthesia. Clinical Trial Registration Number The Chinese Clinical Trial Registry (ChiCTR-INR-17012545).