Background: Prior evidence suggests that caregiving may increase risk of cardiovascular disease (CVD) onset. This association has never been examined in a nationally (USA) representative sample, and prior studies could not fully control for socioeconomic confounders. This paper seeks to estimate the association between spousal caregiving and incident CVD in older Americans. Methods: Married, CVD-free Health and Retirement Study respondents aged 50+ years (n=8472) were followed up to 8 years (1669 new stroke or heart disease diagnoses). Current caregiving exposure was defined as assisting a spouse with basic or instrumental activities of daily living ≥14 h/week according to the care recipients' report in the most recent prior biennial survey; we define providing ≥14 h/week of care at two consecutive biennial surveys as 'long-term caregiving'. Inverse probability weighted discrete-time hazard models with time-updated exposure and covariate information (including socioeconomic and cardiovascular risk factors) were used to estimate the effect of caregiving on incident CVD. Results: Caregiving significantly predicted CVD incidence (HR=1.35, 95% CI 1.06 to 1.68) in the population overall. Long-term caregiving was associated with double the risk of CVD onset (HR=1.95, 95% CI 1.19 to 3.18). This association for long-term care givers varied significantly by race (p<0.01): caregiving predicted CVD onset for white (HR=2.37, 95% CI 1.43 to 3.92) but not for non-white (HR=0.28, 95% CI 0.06 to 1.28). Conclusions: Spousal caregiving independently predicted risk of CVD in a large sample of US adults. There was significant evidence that the effect for long-term care givers differs for non-whites and white.