Please cite this paper as: Saucedo M, Deneux-Tharaux C, Bouvier-Colle M. Understanding regional differences in maternal mortality: a national case-control study in France. BJOG 2012;119:573-581. Objectives To assess the risk of postpartum maternal death associated with region, and to examine whether the quality of care received by the women who died differed by region. Design A national case-control study. Setting France. Population Selected from recent nationwide surveys, 328 postpartum maternal deaths from 2001 through 2006 as cases; and a representative sample (n = 14 878) of women who gave birth in 2003 as controls. Methods Crude and adjusted odds ratios (aOR) of maternal death associated with region were calculated with logistic regression, and the quality of care for women who died was compared according to region with chi-square tests or Fisher's exact tests. Main outcome measures Risk of postpartum maternal death associated with region, and quality of care. Results After adjustment for maternal age and nationality, the risk of maternal death was higher in the Ile-de-France region (aOR 1.6, 95% CI 1.2-2.0) and the overseas districts (aOR 3.5, 95% CI 2.4-5.0) than in the group for the rest of continental France. In both regions, the excess risk of death from haemorrhage, amniotic fluid embolism and hypertensive disorders was significant. In continental France, after further controlling for women's obstetric characteristics, the risk of maternal death in Ile-de-France remained higher (aOR 1.8. 95% CI 1.3-2.6). The women in the cases groups received suboptimal care more frequently in Ile-de-France than in the other continental regions (64% versus 43%, P = 0.01). Conclusions These results suggest that quality of care and organisation of health services may play a role in the differential risk of maternal mortality between regions in France. Research on severe maternal morbidity and its determinants is needed to clarify the mechanisms involved.