Introduction Findings that African-American race/ethnicity is associated with higher concentrations of serum urate have not been adjusted for possible confounding factors or have not explored this question as a primary outcome. We tested this hypothesis in a bi-racial cohort of younger African-American and white men and women. Methods Data from 5,049 participants at the Coronary Artery Risk Development in Young Adults (CARDIA) cohort baseline (1985 to1986) and follow-up for up to 20 years of individuals without hyperuricemia (defined as a serum urate of 6.8 mg/dL or more) at baseline were utilized. We determined associations between race, serum urate and the development of hyperuricemia in sex-specific cross-sectional and longitudinal analyses. Confounding factors examined included: age at enrollment, body mass index, development of hypertension, glomerular filtration rate, medication use, diet and alcohol intake and menopausal symptoms in women. Results Referent to whites, African-American men and women had significantly lower concentrations of serum urate at baseline. African-American men had an essentially equal risk of developing incident hyperuricemia during follow-up compared with white men (multivariable adjusted HR = 1.12 (0.88 to1.40)). African-American women developed a significantly increased risk of hyperuricemia when compared to white women (HR = 2.31 (1.34 to 3.99)). Conclusions Young African-American men and women had lower concentrations of serum urate than whites. During longitudinal follow-up, African-American women had a significantly increased risk of developing hyperuricemia when compared with white women, a difference that was not observed in men. Differences in production of serum urate or a more rapid decline in fractional excretion of serum urate are potential, albeit still unproven, explanations for these findings in African-American women.