The aim of the study was to assess, using population-based data, trends and regional variations in multiple births during the period of increasing use and changes in practice patterns for infertility treatments. National data for 24,554,977 births (live births and stillbirths) were used, including 569,423 twins during the period 1972 to 2003, and 14,599 triplets for 1984 to 2003. Statistical analyses included age-adjusted hierarchical logistic regression models for twin births and separate analyses for triple, same-sex, and different-sex twin births. Due to confidentiality considerations, the only variable available for adjustment was maternal age. Regionallevel variations were estimated using median odds ratios based on random-intercept hierarchical logistic regression models. Overall, twin births increased from 18.1 per 1000 births (95% confidence interval [CI] 17.9–18.2) in 1972 to 1975 to 29.9 per 1000 (95% CI 29.7–30.1) in 2000 to 2003. Twin births increased progressively across all regions, whereas triple births reached a peak in the early 1990s and decreased thereafter. Trends for both twin and triple births varied significantly across regions. Both trends and regional variations were greater for different-sex as compared with same-sex twin births. Regional variations in the proportion of multiple births increased in the case of twin births and decreased for triple births. Differences in multiple births at the regional level in France were comparable to country-level differences observed across several western and northern European countries. Regional differences in multiple births need to be monitored and used to inform policies aimed at regulating the use of infertility treatments.