Background: After the 2009 pandemic, a re-emergence of hemagglutinin type 1 and neuraminidase type 1 (H1N1) influenza cases has been noted in India recently. The number of swab-positive cases has increased in the year 2017 compared to yesteryears. Since the current circulating strain (A/Michigan/7/2009 [H1N1] pdm09) is different from previous pandemic strains, a look into the clinical profile is imperative. Aims: The aim is to study the clinical, biochemical, and radiological profile of H1N1 patients at initial presentation and its influence on the mode of treatment and outcome. Patients and Methods: A cross-sectional record-based analysis of all confirmed cases of H1N1 influenza admitted at Lourdes Hospital, Kochi, Kerala, between 2015 and 2017. Confirmation of cases was done by reverse transcriptase polymerase chain reaction of respiratory specimens at Manipal Centre for Virus Research. Results: A total of 76 confirmed cases of H1N1 influenza were detected during the study period of which 36 required Intensive Care Unit admission. Most patients were between 51 and 60 years (25%). The predominant presenting symptoms were fever (98.7%), dry cough (61.8%), breathlessness (53.9%), and the most common auscultatory finding being bilateral crepitations (64.47%). Around 32.89% of cases presented with bilateral lung infiltrates on X-ray. Sixty-nine of 76 patients (90.79%) survived the disease. Conclusions: Vaccination, early recognition of the disease, and prompt initiation of treatment seem to be the only way to reduce H1N1 disease progression and associated mortality. Patients with risk factors require additional attention as clinical course can be unpredictable. Pregnancy is associated with higher rate of complications. Early respiratory support helped in preventing progression to respiratory failure in most of our patients.