Seventy-two patients scheduled for a unilateral total knee arthroplasty were randomized to receive a sublingual sufentanil tablet system (15mcg) or oral oxycodone for post-operative pain management, in addition to a standardized multimodal analgesia protocol. The primary outcome of interest was pain on a numeric rating scale (NRS) at 24 hours post-operation. Secondary outcomes of interest included NRS pain scores up to 48 hours post-operation, success of first mobilization, incidence of nausea, incidence of vomiting, piritramide consumption in the post-anesthesia care unit (PACU), and patient satisfaction on a Patient Global Assessment (PGA) scale. Results revealed that the median NRS pain scores at rest and during movement at 24 hours were not statistically significantly different between the sufentanil and oxycodone groups (p=0.272; p=0.059). No statistical differences in the incidence of nausea (p=0.181) or vomiting (p=0.69) were observed between the two groups. Additionally, no statistical differences in the time to first mobilization, nor piritramide consumption, were observed between sufentanil and oxycodone groups. A greater proportion of patients in the sufentanil group were satisfied with pain control compared to the oxycodone group (p=0.007).