Résumé : Background: Despite widespread utilization of influenza vaccines, effectiveness (VE) has not been routinely measured in Latin America. Methods: We used a case test-negative control design to estimate trivalent inactivated influenza VE against laboratory-confirmed influenza among hospitalized children aged 6 months-5 years and adults aged ≥60 years which are age-groups targeted for vaccination. We sought persons with severe acute respiratory infections (SARI), hospitalized at 71 sentinel hospitals in Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Honduras, Panama, and Paraguay during January–December 2013. Cases had an influenza virus infection confirmed by real-time reverse transcription PCR (rRT-PCR); controls had a negative rRT-PCR result for influenza viruses. We used a two-stage random effects model to estimate pooled VE per target age-group, adjusting for the month of illness onset, age and preexisting medical conditions. Results: We identified 2620 SARI patients across sites: 246 influenza cases and 720 influenza-negative controls aged ≤5 years and 448 cases and 1206 controls aged ≥60 years. The most commonly identified subtype among participants (48%) was the influenza A(H1N1)pdm09 virus followed by influenza A(H3N2) (34%) and influenza B (18%) viruses. Among children, the adjusted VE of full vaccination (one dose for previously vaccinated or two if vaccine naïve) against any influenza virus SARI was 47% (95% confidence interval [CI]: 14–71%); VE was 58% (95% CI: 16–79%) against influenza A(H1N1)pdm09, and 65% (95% CI: −9; 89%) against influenza A(H3N2) viruses associated SARI. Crude VE of full vaccination against influenza B viruses associated SARI among children was 3% (95% CI: −150; 63). Among adults aged ≥60 years, adjusted VE against any influenza SARI was 48% (95% CI: 34–60%); VE was 54% (95% CI: 37–69%) against influenza A(H1N1)pdm09, 43% (95% CI: 18–61%) against influenza A(H3N2) and 34% (95% CI: −4; 58%) against B viruses associated SARI. Conclusion: Influenza vaccine provided moderate protection against severe influenza illness among fully vaccinated young children and older adults, supporting current vaccination strategies.