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Background: Regional nerve blocks have attained a popularity for total knee arthroplasty (TKA) because they can anesthetize a wider area with a prolonged postoperative analgesic effect. This clinical trial compared postoperative pain control using popliteal plexus blockade (PPB) and fascia iliaca block (FIB) in cases of TKA. Methodology: This double-blinded randomized clinical trial enrolled 60 patients planned for unilateral, primary TKA under spinal anesthesia. Participants were randomly allocated to either the PPB group or the FIB group. The blocks were performed at the end of surgery. Postoperative pain was measured on Numeric Rating Scale (NRS) during rest, and on arrival in PACU, then at 1, 2, 4, 8, and 24 h. Time to first rescue, total morphine consumption and any complications / side-effects were noted in both groups. Results: Numeric rating scale (NRS) scores at 8 h and 12 h during rest, and at 4 h, 8 h, and 12 h during movement were significantly lower in the FIB group than in the PPB group. Morphine consumption in the first 24 h postoperative was significantly lower in the FIB group than in the PPB group. Time to first rescue was delayed significantly in the FIB group than PPB group. Rehabilitation was comparable between the two groups. Patient satisfaction, postoperative nausea and vomiting, hypotension, and bradycardia were comparable between both groups. Conclusions: Fascia iliaca block was superior to popliteal plexus blockade in controlling postoperative pain after total knee arthroplasty, as evidenced by lower pain scores, lesser postoperative morphine consumption, and delayed time to first analgesic request with comparable minimal adverse events. [ABSTRACT FROM AUTHOR]