Background—In French Guiana, the rate of preterm birth remains high despite efforts to reduce it. However, despite progress, perinatal mortality, which is often associated with preterm birth, remains a major cause of premature death in French Guiana. The objective of this study was to analyze prematurity over time and across regions, by type (overall prematurity, extreme prematurity, spontaneous prematurity, induced prematurity), and to identify risk factors in the Guyanese context. Methodology—A retrospective descriptive and comparative study was conducted using data from the 2013–2014 Computerized Pregnancy Outcome Registry (RIGI), which documented 12,983 live births across all four healthcare facilities in the department. These data were supplemented by a case-control study on extreme preterm birth at the Andrée Rosemon Hospital in Cayenne (the region’s only Type 3 maternity facility) from February 2016 to January 2017. Results—The proportion of preterm births was 13.5% (1,755 out of 12,983), of which 51.3% were spontaneous preterm births compared to 48.7% induced preterm births. There was significant spatial heterogeneity between western French Guiana and isolated areas, where preterm births were more frequent. Just over half (57.2%) of the study population had Social Security coverage, and 9.3% had no social security coverage. The absence of social security coverage was a risk factor for preterm birth with an adjusted OR of 1.9 [95% CI=1.6–2.3], p<0.001. The absence of prenatal care was associated with a doubling of the risk of preterm birth, with an adjusted OR of 2 [95% CI=1.2–3.5], p=0.007. Furthermore, regarding pregnancy-related conditions, preeclampsia was the primary condition associated with the risk of preterm birth (adjusted OR of 6.7 [95% CI=5.6–8.1], p=0.001). The case-control study showed that lack of health insurance was also a risk factor for extreme preterm birth, but only for spontaneous preterm birth. In contrast, a history of preterm births was a risk factor for both induced and spontaneous preterm birth. Pregnancy-related conditions, such as hypertension, preeclampsia, placenta previa, and IUGR, were exclusively risk factors for induced preterm birth. Gardnerella vaginalis and Group B streptococcus were risk factors for induced preterm birth but not for spontaneous preterm birth. Conclusion—Social risk factors and poor prenatal care were associated with spontaneous preterm birth. The significance of preeclampsia as a risk factor for induced very preterm birth in French Guiana appears to be significantly greater than elsewhere for reasons that remain unknown.