Purpose Uterine fibroids are the most common benign tumors in reproductive-age women. Factors associated with this condition such as psychosocial stress are still being elucidated. This paper explores the association between major life events (MLE) stress and fibroids. Methods Prevalence ratios (PR) and 95% confidence intervals (CI) were used to determine the association between MLE stress (number of events and stress intensity) and fibroids in 556 Black and 373 White women in the Uterine Fibroid Study, 1996–1999. Main Findings Fibroids were prevalent in 74% and 50% of the Black and White women, respectively. The mean number of MLE reported by each race group was two. Among White women, the PR for those who reported at least one event compared with those with no events were significant after adjusting for age and study identified fibroid risk factors (PR [1 and 2 events], 1.7; 95% CI, 1.2–2.5), (PR [3 events], 1.9; 95% CI, 1.3–2.7), and (PR [4 events], 1.5; 95% CI, 1.0–2.1), respectively. At all levels of stress compared with no events, significant associations with fibroids were found among White women. For Black Women, the PR for fibroids was only significant in the high stress group compared with those without an experienced event, after adjusting for fibroid risk factors (PR, 1.2; 95% CI, 1.1–1.4). Conclusion Examining the number and stress intensity of MLE enriched our understanding of this stressor and fibroids. Further research is needed to understand the role of stress on fibroids among women.