BACKGROUND: Dolutegravir (DTG), a new antiretroviral drug, is being integrated into antiretroviral regimens for people with human immunodeficiency virus (PWH) in Ghana. There is little evidence of the effect of DTG on blood pressure (BP) levels in sub-Saharan Africa, especially West Africa. Our aim was to assess the incidence and predictors of hypertension (HTN) among PWH initiated on a DTG-based antiretroviral regimen in Ghana. METHODS: An observational multicenter longitudinal study was conducted among PWH in Ghana from 2020 to 2022. BPs of nonhypertensive patients with BP ≤120/80 mm Hg at baseline were measured at 3, 6, 12, and 18 months post-DTG initiation. The primary outcome of the study was incidence of HTN, defined as BP ≥140/90 mm Hg. Kaplan-Meier estimator was used to estimate risk of developing HTN. Cox proportional hazards model with robust standard errors was used to estimate hazard ratios (HRs). RESULTS: HTN prevalence among PWH screened was 37.3% (1366/3664). The incidence of de novo HTN among nonhypertensive PWH at 72 weeks was 598.4 per 1000 person-years (PY) (95% confidence interval [CI], 559.2-640.3) with incidence proportion of 59.90 (95% CI, 57.30-62.44). A quarter of those with de novo HTN developed it by month 6. Obesity (adjusted HR [aHR], 1.27 [95% CI, 1.05-1.54]), abnormal serum urea (aHR, 1.53 [95% CI, 1.27-1.85]), and low high-density lipoprotein (aHR, 1.45 [95% CI, 1.22-1.72]) were risk factors for HTN. CONCLUSIONS: Incidence of HTN was high among PWH on DTG. There is a need to monitor BP for HTN in adult PWH as well as traditional risk factors to reduce the burden of HTN and its complications.