Background: Acute poisonings (AP) are a significant public health problem, accounting for a high number of emergency department visits and thousands of deaths worldwide. This study aimed to assess the epidemiology of AP in an adult population admitted to Cayenne Hospital (French Guiana) and to investigate the clinical and sociodemographic characteristics. Methods: We conducted a monocentric retrospective study from January 2010 to December 2022, including patients over eighteen years of age who had been admitted to the emergency department of Cayenne Hospital for acute poisoning. Results: We included 425 patients. The median age was 34 years (IQR: 25–47). The sex ratio (M/F) was 0.52. A psychiatric disorder was found in 41.9% of patients. The Poisoning Severity Score (PSS) on admission was 1 or 2 for 84% of patients, and the mortality rate was 3.9%. The main involved toxicants were psychotropic drugs (43.1%), benzodiazepines (34.8%), and paracetamol (25.6%). The most lethal toxic was paraquat (5.2%). Intoxication was due to intentional self-poisoning in 84.2% of cases. Independent factors associated with severe poisoning (PSS 3 or 4) were chloroquine, neuroleptics, or paraquat poisoning; metabolic acidosis; and hyperglycemia (>5.5 mmol/L). The mortality rate was 3.9%, and the most involved toxic in death was paraquat. Conclusion: This study shows the frequent and deadly use of paraquat in APs in French Guiana. Urgent attention should be given to establishing a toxicovigilance monitoring framework and an antipoison center in the region.