Background and Objectives: Patients undergoing major elective ankle surgery often experience pain from the saphenous nerve territory persisting beyond the duration of a single-injection saphenous nerve block. We hypothesized that perineural dexamethasone as an adjuvant for the saphenous nerve block prolongs the duration of analgesia and postpones as well as reduces opioid-requiring pain. Methods: Forty patients were included in this prospective, randomized, controlled study. All patients received a continuous sciatic catheter and were randomized to receive a single-injection saphenous nerve block with 10 mL of 0.5% bupivacaine with 1:200,000 epinephrine with addition of 1 mL of saline or 1 mL of 0.4% (ie, 4 mg) dexamethasone. The primary outcome was duration of saphenous nerve block estimated as the time until the first opioid request. Secondary outcomes were opioid consumption and pain. Results: The mean (SD) duration of the saphenous nerve block until first opioid request was 29.4 (8.4) hours in the dexamethasone group and 23.2 (10.3) hours in the control group (P = 0.048). Themedian opioid consumption [interquartile range] during the first 24 hours was 0 mg [0-0] versus 1.5 mg [0-14.2] in the dexamethasone and control groups, respectively. Nonparametric comparison of opioid consumption from 0 to 24 hours was statistically significant. The opioid consumption was similar in the two groups in the time interval 24 to 48 postoperative hours. Conclusion: Perineural dexamethasone as an adjuvant for the singleinjection subsartorial saphenous nerve block can prolong analgesia and reduce opioid-requiring pain after major ankle surgery.