ImportanceFertility status is a marker for future health, and infertility has been associated with risk for later cancer and diabetes, but associations with midlife cardiovascular health (CVH) in female individuals remain understudied.ObjectiveTo evaluate the association of infertility history with CVH at midlife (approximately age 50 years) among parous individuals.Design, Setting, and ParticipantsProject Viva is a prospective cohort study of pregnant participants enrolled between 1999 and 2002 who delivered a singleton live birth in the greater Boston, Massachusetts, area. Infertility history was collected at a midlife visit between 2017 and 2021, approximately 18 years after enrollment. Data analysis was performed from January to June 2023.ExposuresThe primary exposure was any lifetime history of infertility identified by self-report, medical record, diagnosis, or claims for infertility treatment.Main Outcomes and MeasuresThe American Heart Association’s Life’s Essential 8 (LE8) is a construct for ranking CVH that includes scores from 0 to 100 (higher scores denote better health status) in 4 behavioral (diet, physical activity, sleep, and smoking status) and 4 biomedical (body mass index, blood pressure, blood lipids, and glycemia) domains to form an overall assessment of CVH. Associations of a history of infertility (yes or no) with mean LE8 total, behavioral, biomedical, and blood biomarker (lipids and glycemia) scores were examined, adjusting for age at outcome (midlife visit), race and ethnicity, education, household income, age at menarche, and perceived body size at age 10 years.ResultsOf 468 included participants (mean [SD] age at the midlife visit, 50.6 [5.3] years) with exposure and outcome data, 160 (34.2%) experienced any infertility. Mean (SD) LE8 scores were 76.3 (12.2) overall, 76.5 (13.4) for the behavioral domain, 76.0 (17.5) for the biomedical domain, and 78.9 (19.2) for the blood biomarkers subdomain. In adjusted models, the estimated overall LE8 score at midlife was 2.94 points lower (95% CI, −5.13 to −0.74 points), the biomedical score was 4.07 points lower (95% CI, −7.33 to −0.78 points), and the blood subdomain score was 5.98 points lower (95% CI, −9.71 to −2.26 points) among those with vs without history of infertility. The point estimate also was lower for the behavioral domain score (β = −1.81; 95% CI, −4.28 to 0.66), although the result was not statistically significant.Conclusions and RelevanceThis cohort study of parous individuals found evidence for an association between a history of infertility and lower overall and biomedical CVH scores. Future study of enhanced cardiovascular preventive strategies among those who experience infertility is warranted.