Background The latest influenza pandemic intensified the interest in this infection. Objective We aimed to compare the characteristics of outpatients with seasonal and pandemic influenza. Methods We retrospectively reviewed data regarding outpatients that sought medical advice from a network of physicians performing house-call visits at the area of Attica, Greece, that underwent a direct influenza test during the period of seasonal influenza (1/1/2009-1/5/2009), and 2009 H1N1 pandemic influenza period (17/5/2009-15/4/2010). Results A total of 195 and 1317 patients had a direct influenza test during the seasonal and pandemic influenza period, respectively; 50.7% and 32% of these patients had a positive test result for influenza, respectively. Viral culture or polymerase chain reaction (PCR) were not implemented. Patients found positive for influenza during the pandemic period, compared to those evaluated during the seasonal period, were younger (mean age ± SD: 33 ± 17.2 vs 38.2 ± 19.2, p=0.008), more likely to have no comorbidity (62.9% vs 45.5%, p=0.002), had milder clinical manifestations, and were treated with more antibiotics (38.3% vs 9.9%, p<0.001). However, patients found positive during the seasonal period were treated with more antivirals (oseltamivir: 69.1% vs 85.7%, p=0.006). No difference was observed regarding the need for immediate hospitalization. These findings were, consistent in the complementary analysis involving patients tested for influenza during the compared periods. Conclusion Despite the methodological limitations, our findings suggest that patients with pandemic influenza were younger, had milder clinical manifestations, and were less likely to have any kind of comorbidity, compared to patients with seasonal influenza.