144 patients who were undergoing primary unilateral total knee arthroplasty (TKA) were randomized to receive wound infiltration with DepoFoam bupivacaine (133 mg, 266 mg, 399 mg or 532 mg) or bupivacaine HCl with epinephrine. Over 5 days, the DepoFoam bupivacaine groups had significantly lower pain scores at rest than the bupivacaine HCl group at several time periods. On day 5, the cumulative pain score at rest was significantly lower in the DepoFoam 532 mg group than in the bupivacaine HCl group. On day 8, the blinded care provider was also significantly more satisfied with the DepoFoam 532 mg group than with the bupivacaine HCl group. There were no other significant differences between the groups.