We conducted a retrospective study to compare clinical and laboratory findings between 1) severe influenza A and mild influenza A and 2) pandemic 2009 H1N1 (pdm09 A/H1) and seasonal H3N2 (A/H3) from 2009 to 2010. A total of 526 (mean age, 13.6 years; 447 pdm09 A/H1, 79 seasonal A/H3) patients were included, 41 (7.8%) with severe influenza (mean age, 28.1 years; 26 pdm09 A/H1, 15 seasonal A/H3). Influenza-associated complications were pneumonia (75.6%), meningoencephalitis (14.6%), acute kidney injury (14.6%), and acute respiratory distress syndrome (12.2%). Patients with seasonal A/H3 were significantly less likely to experience sore throat (P < 0.001), malaise (P < 0.001), and muscle pain (P < 0.001); they were significantly more likely to have hypertension (P < 0.001), diabetes mellitus (P = 0.001), and chronic obstructive pulmonary disease (P < 0.001), delayed hospital presentation (P = 0.001), delayed oseltamivir treatment (P < 0.001), and higher in-hospital mortality (P = 0.02) than patients with pdm09 A/H1. Further comparison between severe pdm09 A/H1 and severe seasonal A/H3 revealed that severe seasonal A/H3 patients (median age, 71 years) were significantly older than patients with severe pdm09 A/H1 (median age, 7 years) (P < 0.001). Comparison between severe influenza and mild influenza, regardless of influenza A subtypes, by multivariate analysis, found that tachypnea (odds ratio [OR] = 44.3, 95% confidence interval [CI] = 15.7-124.6) and delayed oseltamivir therapy ≧ 48 hours after illness onset (OR = 3.7, 95% CI = 1.3-10.5) were independent risk factors for severe influenza. The findings of this study will improve the understanding of the clinical differences between pdm09 A/H1 and seasonal A/H3, and of influenza-associated complications and predictors for severe outcomes that can help to direct clinicians toward the most effective management of influenza patients to reduce the preventable mortality and morbidity.