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Exploring time-to-onset of efficacy of the live-attenuated dengue vaccine TAK-003 is important for individuals living in, or traveling to, dengue-endemic areas. This protocol-defined exploratory analysis of the Tetravalent Immunization against Dengue Efficacy Study (TIDES) investigated TAK-003's onset of efficacy after the first and before the second dose, administered 3 months later, in healthy participants aged 4-16 years randomly assigned 2:1 to receive TAK-003 or placebo. The number of virologically confirmed dengue (VCD) cases between first and second vaccinations and the time-to-onset of vaccine efficacy (VE) were assessed in the safety population. Fifty VCD cases occurred between the first and second doses (placebo = 37, TAK-003 = 13). The VE against VCD up to 3 months after the first dose was 82.1 %, with an estimated time-to-onset of ∼14 days. TAK-003 provides rapid onset of protection after the first dose and may be useful in the context of a dengue outbreak or as a travel vaccine.