Impaired surgical site healing occurs in 20% to 50% of sirolimus (SRL)-treated renal transplant (RT) recipients, with most patients having received concomitant corticosteroids. We determined the incidence of surgical site complications among RT recipients receiving SRL with mycophenolate mofetil (MMF), with most patients on a steroid-avoidance protocol. SRL/MMF patients with complications within 3 months of transplantation were compared with 1) SRL/MMF patients without them and 2) matched RT recipients receiving tacrolimus (FK)/MMF. Between January 2002 and March 2005, 44 of 300 (15%) RT recipients received SRL within 6 weeks of transplantation. Fourteen (31.8%) developed lymphocele, bladder leak, wound dehiscence, cellulitis, or an abscess. Obesity (BMI > or =30 kg/m2) was significantly associated with problems: the mean BMI of SRL cases with complications was 29.9 kg/m2 vs 25.4 kg/m2 for SRL patients without them (P = .047). Seventy-one percent of obese SRL patients experienced complications compared with 24.3% (P = .025) of non-obese SRL patients. Surgical treatment was required in 29% of patients. Rates of maintenance steroid use were similar in SRL complicated cases compared with SRL patients without them. The FK control group showed a lower rate of complications (14.3%; P = .163) despite similar BMI, rejection rates, and chronic steroid use as the SRL group. Obesity and graft rejection were independent predictors of complications. Thus, among a group of predominantly steroid-free recipients on SRL, the rates of wound complications were similar to those seen previously, but the highest risk for them was observed in obese recipients and in those with acute rejection episodes. Wound complications were associated with significant morbidity.