BackgroundClinical differentiation of influenza from dengue and other febrile illnesses (OFI) is difficult, and available rapid diagnostic tests have limited sensitivity.MethodsWe conducted a retrospective study to compare clinical and laboratory findings between (i) influenza and dengue and (ii) influenza and OFI.ResultsOf 849 enrolled patients, the mean time between illness onset and hospital presentation was 1.7, 3.7, and 3 days for influenza, dengue, and OFI, respectively. Among pediatric patients (â€18 years) (445 influenza, 24 dengue, and 130 OFI), we identified absence of rashes, no leukopenia, and no marked thrombocytopenia (platelet counts <100 Ă 109 cells/L) as predictors to distinguish influenza from dengue, whereas rhinorrhea, malaise, sore throat, and mild thrombocytopenia (platelet counts 100-149 Ă 109/L) were predictors that differentiated influenza from OFI. Among adults (>18 years) (81 influenza, 124 dengue, and 45 OFI), no leukopenia and no marked thrombocytopenia distinguished influenza from dengue, while rhinorrhea and malaise differentiated influenza from OFI. A diagnostic algorithm developed to distinguish influenza from dengue using rash, leukopenia, and marked thrombocytopenia showed >90% sensitivity to identify influenza in pediatric patients.ConclusionsThis study identified simple clinical and laboratory parameters that can assist clinicians to distinguish influenza from dengue and OFI. These findings may help clinicians diagnose influenza and facilitate appropriate management of affected patients, particularly in resource-poor settings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0623-z) contains supplementary material, which is available to authorized users.