One hundred and fifty patients scheduled for an acute ankle fracture surgery were randomized to receive peripheral nerve blockade (popliteal sciatic nerve block; saphenous nerve block; n=77) or spinal anesthesia (n=73). The primary outcome of interest was post-operative pain measured using the Pain Intensity and Opioid Consumption (PIOC) score, a composite of Numeric Pain Rating (NRS) area under the curve pain score and total morphine consumption. Secondary outcomes of interest included NRS area under the curve, morphine consumption, quality of recovery (QoR-15) score, opioid adverse events on the opioid related symptom distress score (OR-SDS), number of patients at risk of post-operative pain, patient satisfaction, and adverse events. Outcomes were assessed up to 27 hours post-operation. Results revealed significantly lower PIOC scores, morphine consumption, and NRS area under curve pain scores in the peripheral nerve block group compared to the spinal anesthesia group (p<0.05 for all). Moreover, the incidence of opioid adverse events on post-operative day 2 and the number of patients at risk of post-operative pain were significantly lower in the peripheral nerve block group (p=0.001). No significant differences in the incidence of adverse events were observed between the two groups (p=0.075).