Hypertension is associated with cardiovascular disease in the human immunodeficiency virus (HIV)–infected population. The authors aimed to test the hypothesis whether advanced immunosuppression with low nadir CD4 lymphocyte cell count is a predictor of sustained hypertension in HIV-infected individuals. In a longitudinal study of an HIV cohort of 434 patients (43±11 years, 72% men, 71% Caucasians), standardized blood pressure was measured in duplicate during 3 clinical visits both at baseline and after 3.4±0.8 years. The lowest CD4 cell count in the individual history was recorded as nadir CD4. Both nadir CD4 cell count <50 cells/μL and duration of antiretroviral therapy (ART) were associated with sustained hypertension, and the highest proportion of hypertensive patients was observed in those who had both nadir CD4 cell count <50 cells/μL and prolonged ART duration. Nadir CD4 cellcount <50 cells/μL was an independent predictor of hypertension (adjusted odds ratio [OR], 2.48; 95% confidence interval [CI], 1.27–4.83), as was ART duration (adjusted OR, 1.13; 95% CI, 1.03–1.24). The predictive power of ART duration was more pronounced in patients with nadir CD4 cell count <50 cells/μL. Delaying ART initiation until a state of advanced immunosuppression might add to and even fuel the cardiovascular risk associated with ART. J Clin Hypertens (Greenwich). 2012; 00:00–00 ©2012 Wiley Periodicals, Inc.