Reliable and rapid diagnosis of influenza A H1N1 is essential to initiate appropriate antiviral therapy and preventive measures. We analysed the differences in clinical presentation and laboratory parameters between emergency department patients with PCR‐confirmed H1N1 influenza infection (n = 199) and those with PCR‐negative influenza‐like illness (ILI; n = 252). Cough, wheezing, leucopenia, eosinopenia and a lower C‐reactive protein remained significant predictors of H1N1 influenza. Proposed combinations of clinical symptoms with simple laboratory parameters (e.g. reported or measured fever and either cough or leucocytes <8.5 × 109/L) were clearly superior to currently used official ILI case definitions that use clinical criteria alone.