This study evaluated the efficacy of a tetravalent dengue vaccine (CYD-TDV) in children aged 9 to 16 years in five Latin American countries where dengue is endemic. A total of 20,869 healthy children were randomly assigned to receive either three doses of the vaccine or placebo at 0, 6, and 12 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD) occurring more than 28 days after the third injection. The vaccine demonstrated a per-protocol efficacy of 60.8% (95% CI, 52.0 to 68.0) and an intention-to-treat efficacy of 64.7% (95% CI, 58.7 to 69.8). Serotype-specific efficacy was observed, with the highest efficacy against serotype 4 (74.0%) and the lowest against serotype 2 (42.3%). The vaccine also showed high efficacy against severe dengue (95.5%) and hospitalization for dengue (80.3%). The safety profile was similar to that of the placebo, with no significant differences in adverse events. The study concluded that the CYD-TDV vaccine is effective in preventing symptomatic and severe dengue and reducing hospitalizations in children in endemic regions.This study evaluated the efficacy of a tetravalent dengue vaccine (CYD-TDV) in children aged 9 to 16 years in five Latin American countries where dengue is endemic. A total of 20,869 healthy children were randomly assigned to receive either three doses of the vaccine or placebo at 0, 6, and 12 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD) occurring more than 28 days after the third injection. The vaccine demonstrated a per-protocol efficacy of 60.8% (95% CI, 52.0 to 68.0) and an intention-to-treat efficacy of 64.7% (95% CI, 58.7 to 69.8). Serotype-specific efficacy was observed, with the highest efficacy against serotype 4 (74.0%) and the lowest against serotype 2 (42.3%). The vaccine also showed high efficacy against severe dengue (95.5%) and hospitalization for dengue (80.3%). The safety profile was similar to that of the placebo, with no significant differences in adverse events. The study concluded that the CYD-TDV vaccine is effective in preventing symptomatic and severe dengue and reducing hospitalizations in children in endemic regions.