Background: After the 2009 influenza pandemic the H1N1pdm09 strain circulate seasonally. In 2015, Puerto Montt Hospital in Chile faced a simultaneous outbreak of both seasonal H3N2 and H1N1pdm09 influenza A (IA). Aim: To evaluate the clinical differences between the two viral strains and recent changes in the behavior of H1N1pdm09 IA. Material and Methods: We set up a retrospective study including every adult hospitalized in Puerto Montt Hospital in 2015 due to IA, confirmed by reverse transcription polymerase chain reaction. We compared epidemiological data, clinical presentation, complications, and the outcome of patients with H1N1pdm09 versus those with seasonal influenza. In parallel, we compared 62 cases of thatH1N1 IA from 2015 with 100 cases who were hospitalized and analyzed in 2009. Results: Between July and October 2015, 119 adults with confirmed IA were hospitalized. From 2009 to 2015, the mean age of patients with IAH1N1pdm09 increased from 40.4 +/- 17 to 58.8 +/- 16 years (p < 0.01). Pneumonia as the cause of hospitalization decreased from 75 to 58% of patients, (p = 0.04). Likewise, the presence of comorbidities increased from 53 to 74%, (p < 0.01). Compared with seasonal H3N2, patients with IAH1N1pdm09 IA were more likely to require intensive care (p < 0.01) and mechanical ventilation (p < 0.01) and developed septic shock (p = 0.03). Their mortality was non-significantly higher (13 and 5% respectively). Conclusions: The clinical presentation of H1N1pdm09 IA has varied over time and now affects an older population, with a greater number of comorbidities. It also appears to be adopting the clinical behavior of a classic seasonal influenza virus.