Introduction: During the 2009 influenza pandemic, several reports were published, nevertheless, data on the clinical profiles of critically ill patients with the new virus infection during this second outbreak are still lacking. Material methods: Prospective, observational, multi-center study conducted in 148 Spanish intensive care units (ICU) during epidemiological weeks 50-52 of 2010 and weeks 1 - 4 of 2011. Results: Three hundred patients admitted to an intensive care unit (ICU) with confirmed An/H1N1 infection were analyzed. The median age was 49 years [IQR = 38-58] and 62% were male. The mean APACHE II score was 16.9 +/- 7.5 and the mean SOFA score was 6.3 +/- 3.5 on admission. Comorbidities were present in 76% (n = 228) of cases and 111(37.4%) patients were reportedly obese and 59 (20%) were COPD. The main presentation was viral pneumonia with severe hypoxemia in 65.7% (n = 197) of the patients whereas co-infection was identified in 54 (18%) patients. All patients received antiviral treatment and initiated empirically in 194 patients (65.3%), however only 53 patients (17.6%) received early antiviral treatment. Vaccination was only administered in 22 (7.3%) patients. Sixty-seven of 200 patients with ICU discharge died. Haematological disease, severity of illness, infiltrates in chest X-ray and need for mechanical ventilation were variables independently associated with ICU mortality. Conclusions: In patients admitted to the ICU in the post-pandemic seasonal influenza outbreak vaccination was poorly implemented and appear to have higher frequency of severe comorbidities, severity of illness, incidence of primary viral pneumonia and increased mortality when compared with those observed in the 2009 pandemic outbreak.