Forty-five patients with unilateral TKA were randomized to receive parasacral ischial plane block (PIPB) with liposomal bupivacaine 133 mg (n=22) or 266 mg (n=23). The primary outcome was Numerical Rating Scale (NRS)-area-under-the-curve (AUC) at rest from 0–72 h. Secondary outcomes included NRS-AUC during activity, rescue opioid use (oral morphine equivalents, OME), time to first rescue dose, sensory/motor block onset and regression, rehabilitation metrics, and adverse events, assessed over 72 h (or at predefined time points). Overall, the results revealed lower NRS-AUC at rest with 266 mg vs 133 mg (97.3 vs 132.3; p=0.001), faster sensory and motor block onset (35 vs 60 min; 50 vs 85 min; both p<0.001), and less OME on POD1 (27.2 vs 43.1 mg; p=0.009), with no between-group differences in activity pain, total OME, rehab outcomes, or adverse events. In short, PIPB with 266 mg liposomal bupivacaine provided superior rest analgesia in the first 72 h without added safety concerns.