Background: India reported its first case of 2009 pandemic influenza A (H1N1) virus infection in May 2009 and in Saurashtra region in August 2009. We describe the epidemiology and factors associated with severe and non-severe cases of 2009 influenza A (H1N1) infection reported in Saurashtra region. Materials and Methods: From September 2009 to February 2010, we observed 274 patients who were infected with 2009 influenza A (H1N1) virus and admitted in different hospitals in Rajkot city. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) testing was used to confirm infection. Factors associated with severe disease were determined by comparing with non-severe cases. Results: Out of 274 patients, 87 had severe disease (requiring intensive care or died) and 187 had non-severe diseases (admitted in wards and survived). The median age of severe disease patients was 30 years; the median time was 5 days from the onset of illness to diagnosis, and 4 days median time was reported for hospital stay. More than half of the patients (56.3%) were females, and 58.6% patients were residing in urban area (OR = 1.65, CI = 0.97-2.8), among severe disease patients. Significant association (P < 0.01) was reported among severe disease patients for delayed referral from general practitioner/physician after initial treatment. All patients received antiviral drug, but only 19.5% received the same within 2 days of illness. Presence of coexisting condition [odds ratio (OR) = 0.53, confidence interval (CI) = 0.31-0.90], mainly pregnancy (OR = 0.22, CI = 0.06-0.76), was strongly associated with severe disease. Conclusion: Delayed referral from general practitioner/physician, duration of antiviral treatment, and presence of coexisting condition (especially pregnancy) were responsible for intensive care or mortality in patients of severe influenza A (H1N1) illness.