Background. We followed a cohort of 773 individuals who received a monovalent vaccine against 2009 pandemic influenza A (H1N1). Approximately 6 weeks after vaccination, 12 persons developed the disease. Methods. Three groups of subjects were studied (12 patients who had or had not received previous-monovalent vaccine and 1 group of 49 control subjects who had previously been immunized with the same vaccine). For all patients, clinical features were characterized and the causative viruses sequenced for possible mutations. Nasopharyngeal swabs, serum specimens, and peripheral blood monocyte cells (PBMCs) were collected at different time points up to 11 weeks after symptom onset to measure the virus load and humoral and cellular immune responses. Serum samples and PBMCs were also collected from 49 and 16 vaccinated control subjects, respectively. Results. Both patient groups had similar clinical manifestations. No substantial viral mutations were detected. Compared with unvaccinated patients, viral loads in vaccinated patients were initially higher, but the levels decreased faster to undetectable levels. However, the virus became detectable again for 6 of them. Two weeks after infection, vaccinated and unvaccinated patients had similar neutralizing antibody levels as the vaccinated control subjects. Thereafter, the neutralizing antibody levels decreased markedly in vaccinated patients. During the acute phase, memory T cell counts and tumor necrosis factor-a levels were significantly higher in vaccinated than in unvaccinated patients. Conclusions. Although the clinical consequences of infection are comparable between vaccinated and unvaccinated patients, humoral and cellular immune responses in vaccinated patients are boosted for some weeks, indicating an additional benefit of vaccination against 2009 pandemic influenza A (H1N1) virus.