Background and Purpose: The incidence of postoperative complications in human immunodeficiency virus (HIV)-infected patients remains controversial. Published data suggest that these patients are at higher risk for postoperative surgical site infections (SSIs) than are uninfected patients if the site is contaminated. To determine the incidence of postoperative SSI in HIV-infected patients undergoing aseptic surgery at uncontaminated sites, we performed a prospective case series analysis. We hypothesized that the rate of postoperative SSI would be low for this aseptic procedure, irrespective of CD4+ lymphocyte counts. Additionally, we monitored the rates of other complications, namely, hematoma, dorsal vein thrombosis, epididymitis, lymphocele, and suture extrusion. Methods: From May 1, 2000, through January 31, 2006, we performed 137 sterile inguinal lymph node biopsies in 44 HIV-infected patients as part of a funded study evaluating the role of peripheral lymphatic tissue in the pathophysiology of HIV infection. Postoperatively, we followed all patients for a minimum of 30 days. Results: Postoperatively, we noted one instance each (0.7%) of infection, dorsal vein thrombosis with epididymitis (0.7%), and lymphocele and two cases each (1.4%) of hematoma and suture extrusion. The CD4+ count at the time of biopsy did not correlate with postoperative complications. Conclusions: Inguinal lymph node biopsy in HIV-infected patients is safe, irrespective of CD4+ lymphocyte count.