Since the introduction of highly active antiretroviral therapy (HAART), the frequency of opportunistic disorders (ODs) of the gastrointestinal (GI) tract in human immunodeficiency virus (HIV)-infected patients has fallen dramatically. We have found, however, that despite the use of HAART, HIV-infected patients can still present with GI ODs. To evaluate the prevalence of GI ODs in HIV-infected patients on HAART who were undergoing endoscopie evaluation for GI-related symptoms. From January 1996 through February 2002, all HIV-infected patients undergoing GI endoscopy were prospectively identified; mucosal biopsies were obtained in a standardized fashion and histologic specimens were examined by a single GI pathologist. All the patients on HAART presenting with a GI OD are described. Results showed that 294 patients (88% men; mean age, 36.5 ± 10 years; median CD4 lymphocyte count, 64 cells/μl; range, 1-884; median viral RNA level, 40,357 copies/ml; range, 0-7,721,715) underwent 401 upper and/or lower endoscopies during the study period. The use of HAART increased from 10% in early 1996 to 85% in 2002. Nevertheless we found that 27 patients (9%) presented with a GI OD despite HAART. Forty percent of the patients with a GI OD were noncompliant with HAART. We conclude that GI ODs can occur despite HAART and normal CD4 counts. The prevalence of GI ODs in HIV-infected patients taking HAART is 9%. The reasons for this are multifactorial and likely include noncompliance with medications, viral resistance to the drugs, and decreased drug bioavailability. Although the use of HAART has led to a decreased incidence of GI ODs in AIDS, the gastroenterologist evaluating these patients should not discard the possibility that the GI symptoms in HIV-infected patients taking HAART may be secondary to an OD, even when the CD4 count is nonnal and the viral load is low. © 2005 Springer Science+Business Media, Inc.