ObjectiveInflammation plays an important role in the pathophysiology of hypertension (HTN). Aggregate index of systemic inflammation (AISI), as a new inflammatory and prognostic marker has emerged recently. Our goal was to determine whether there was a relationship between HTN and AISI.MethodsWe analyzed patients with HTN from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The primary end point was cardiovascular mortality. A total of 23,765 participants were divided into four groups according to the AISI quartile level. The association between AISI and cardiovascular mortality in patients with HTN was assessed by survival curves and Cox regression analyses based on NHANES recommended weights.ResultsHigh levels of AISI were significantly associated with cardiovascular mortality in patients with HTN. After full adjustment for confounders, there was no significant difference in the risk of cardiovascular mortality in Q2 and Q3 compared to Q1, while Q4 (HR: 1.91, 95% CI: 1.42–2.58;P< 0.001) had a higher risk of cardiovascular mortality compared to Q1. Results remained similar in subgroup analyses stratified by age (Pfor interaction = 0.568), gender (Pfor interaction = 0.059), and obesity (Pfor interaction = 0.289).ConclusionsIn adults with HTN, elevated AISI levels are significantly associated with an increased risk of cardiovascular mortality and may serve as an early warning parameter for poor prognosis.