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Context: The invasion of the lionfish (Pterois volitans) in the French West Indies represents one of the most important marine invasions by alien species in history. Since its first recognition in Martinique in February 2011, the lionfish presence has strongly progressed, resulting in increasing envenomation cases. Our objective was to report features of lionfish envenomation and outcome., Methods: A prospective study conducted at the Martinique University Hospital by the emergency departments, general practitioners, and the pre-hospital emergency ambulance service included all the patients referred from November 2011 to February 2014 for one or several stings by lionfish, as strongly suggested by the fish description and the association with marked local pain and edema. Recommended management included immersion of the affected body part in hot water at 35-40 °C for 60 min, analgesics, tetanus toxoid, and antibiotics., Results: 117 patients [98M/19F; age: 42 ± 14 years [mean ± SD]; with significant past morbidities (16%)] were included. Envenomation resulted in marked pain and local edema (100%), paresthesia (90%), abdominal cramps (62%), extensive edema (53%), tachycardia (34%), skin rash (32%), gastrointestinal disorders (28%), fainting (27%), transient weakness (24%), hypertension (21%), hypotension (18%), hyperthermia (9%), bradycardia (3%), hypophosphatemia (12%), elevated aspartate aminotransferase (AST) (10%), and thrombocytopenia (3%). The sting was complicated by local infection (18%) including skin abscess (5%), cellulitis (3%), skin necrosis (3%), and septic arthritis (2%). 26 patients (22%) were hospitalized requiring surgery (8%). Lionfish stings were single (81%) or multiple (19%). Localization was preferentially at one upper (67%) or lower limb (32%). All patients actually improved. Based on multivariate analyses, pain duration > 24 h was significantly associated with skin eruption (p = 0.001) and muscle cramps (p = 0.0002). Local infectious complications occurred more frequently in patients presenting multiple stings (p = 0.008). Immersion in hot water (44%, performed less than 3 h after the sting in 36% of the cases) significantly reduced pain duration (p = 0.02) and local infection (p = 0.02)., Conclusion: Lionfish represents a major health threat in Martinique with increasing envenomation and significant morbidities. Outcome is favorable if promptly managed, with possible reduction in pain duration and local infections with the rapid immersion of the stung body part in hot water. Our data encourage the authorities to develop investigations on the exact extent of the lionfish invasion and set up a regional taskforce to inform the ecosystem users and register all lionfish-attributed incidents.