BackgroundAllostatic load (AL) is the physiologic “wear and tear” on the body from stress. Yet, despite stress being implicated in the development heart failure (HF), it is unknown whether AL is associated with incident HF events.MethodsWe examined 16,765 participants without HF at baseline from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The main exposure was AL score quartile. AL was determined according to 11 physiologic parameters, whereby each parameter was assigned points (0–3) based on quartiles within the sample, and points were summed to create a total AL score ranging from 0–33. The outcome was incident HF event. We examined the association between AL quartile (Q1-Q4) and incident HF events using Cox proportional hazards models, adjusted for demographics, socioeconomic factors, and lifestyle.ResultsThe mean age was 64 ± 9.6 years, 61.5% were women, and 38.7% were Black participants. Over a median follow up of 11.4 years, we observed 750 incident HF events (635 HF hospitalizations and 115 HF deaths). Compared to the lowest AL quartile (Q1), the fully adjusted hazards of an incident HF event increased in a graded fashion: Q2 HR 1.49 95% CI 1.12–1.98; Q3 HR 2.47 95% CI 1.89–3.23; Q4 HR 4.28 95% CI 3.28–5.59. The HRs for incident HF event in the fully adjusted model that also adjusted for CAD were attenuated, but remained significant and increased in a similar, graded fashion by AL quartile. There was a significant age interaction (p-for-interaction < 0.001), whereby the associations were observed across each age stratum, but the HRs were highest among those aged < 65 years.ConclusionAL was associated with incident HF events, suggesting that AL could be an important risk factor and potential target for future interventions to prevent HF.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12872-023-03371-z.