BACKGROUND: For people living with HIV in sub-Saharan Africa, antiretroviral therapy (ART) improved life expectancy but resulted in a concomitant increased risk of age-related cardiovascular disease (CVD) multimorbidity. So far, studies examining the relationship between hypertension and HIV and ART status are cross-sectional and lack longitudinal associations. METHODS: A longitudinal analysis was performed on data from the Ndlovu Cohort Study, South Africa, comparing data from HIV-positive and HIV-negative individuals collected annually across a 3-year follow-up period. Linear mixed models were used to estimate trends in systolic and diastolic blood pressure by sex over time according to HIV and ART status. RESULTS: Data was analysed from 1364 participants with a median age of 39 years (SD ± 12.8); 557 (40.8%) were HIV-positive and 764 (56%) were female. A total of 432 HIV-infected individuals were taking ART medication, of whom 78.8% measured an undetectable viral load of <50 cp/mL. The baseline hypertension prevalence (=140/=90 mmHg ) was 20.4% in HIV-negative participants and 10.2% in HIV-positive participants on ART, which increased to 38.7% and 26.6% respectively after 36-months of follow-up. After multivariable adjustment, use of ART medication, but not HIV status, was associated with an 8.41 mmHg lower systolic blood pressure [P==0.001]. Sex-stratified analysis showed classic CVD risk factors were a specific concern for HIV-positive males. CONCLUSIONS: South Africa is faced with a high overall burden of uncontrolled hypertension. There is a need for population-level prevention of factors associated with hypertension and CVD risk, with emphasis on improving health-seeking behaviours in men.