Objective: The objectives of this study are to describe the characteristics of births in French Guiana, to determine the perinatal mortality rate among newborns from different population groups living in French Guiana, and to describe changes in these rates over the study period. Materials and Methods: Births occurring between January 1, 1992, and December 31, 1999, in the department’s maternity wards and health centers were included. Socio-demographic and clinical data were collected at the time of delivery. These data pertain to all births with a birth weight of 500 grams or more or a gestational age of 22 weeks or more from the first missed period. Results: The results of our study show that deliveries at health centers decreased significantly in favor of public maternity hospitals from the 1992–1995 period (5.7% and 69.7%, respectively) to the 1998–1999 period (2.4% and 85.7%, respectively), the result of an antenatal referral policy implemented through a network of birth care professionals. Perinatal mortality decreased significantly between 1995 and 1998, from 35.4% to 15.2% for Creoles (p = 0.06), for Surinamese Black-Brown women from 46% to 16.5% (p < 0.0007), and for French Black-Brown women from 36% to 10.2% (p < 0.009). This decline in mortality among births from high-risk groups may have contributed to the decrease in the crude perinatal mortality rate observed during the study period. While the preterm birth rate remained stable (13.5%) and the proportion of low-birth-weight infants increased only slightly (from 12.8% to 13.7%), mortality among preterm infants decreased significantly, most likely as a result of improvements in neonatal resuscitation. Conclusion: Despite these notable improvements, with a perinatal mortality rate (18.9% in 1999) nearly three times that of mainland France (7.4% in 1994), a high proportion of young mothers (17% are under 20), a high proportion of primiparous women and women with many previous births, and the absence or inadequacy of prenatal care, perinatal health remains a priority public health issue and a major challenge for the future of Guyanese society