OBJECTIVE: Recent studies have reported increased fetal loss and preeclampsia in women with sickle cell trait (hemoglobin [Hb] AS). There is a paucity of studies of outcomes in carriers of hemoglobin C. We examined the prevalence of hemoglobin C and S carrier status (Hb AC and Hb AS, respectively) and their effect on pregnancy outcomes. METHODS: This was a retrospective cohort study using data prospectively collected from 1991 to 2006. Perinatal and maternal outcomes for African-American women with Hb AS and Hb AC were compared with those with normal hemoglobin (Hb AA). Multivariable regression was performed by applying generalized estimating equations to account for correlation between births from the same woman. RESULTS: Among 22,096 eligible African-American women (36,897 pregnancies) with routine antenatal hemoglobin electrophoresis, 88.5% had a normal (Hb AA) pattern. Hemoglobin AS was identified in 8.2% and Hb AC in 2.4% of women. Hemoglobin SS and Hb SC each accounted for less than 0.2% and Hb CC for 0.01%. Prevalence and relative risks for adverse outcomes in 3,019 AS pregnancies (3,062 births) and 875 AC (886 births), compared with 32,724 AA pregnancies (33,213 births), were not increased. Adjusted relative risks (95% confidence intervals) for perinatal mortality and preeclampsia were 0.7 (0.5-1.0) and 1.0 (0.8-1.2), respectively, for AS and 0.7 (0.3-1.4) and 1.0 (0.6-1.3), respectively, for AC. Risks of stillbirths and pregnancy-associated hypertension were also not increased. CONCLUSION: Contrary to other recent reports, perinatal mortality and preeclampsia are not increased in carriers of sickle cell trait or hemoglobin C. © 2007 The American College of Obstetricians and Gynecologists.