Influenza outbreaks are associated with significant morbidity. Our aim was to determine the factors associated with increased mortality in hospitalized patients admitted with diagnosis of influenza, at a tertiary care center in Pakistan. This study included all adult patients with an influenza infection, confirmed by real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) at Aga Khan University Hospital Pakistan. In our study, 112 patients with laboratory-confirmed influenza virus infection were admitted at our hospital from the 1st of January 2013 to the 31st of December 2018. Eighty-nine patients (79.46%) were managed in ward or special care units and 23 patients (20.5%) received treatment in intensive care unit (ICU). The overall mortality in our study was 15/112 (13.4%) with the mortality rate of ICU patients being 47.8% while the mortality rate of patients treated in special care units and wards was only 4.5%. The mean age of patients with influenza infection was 58.1 years (±16.6). Influenza virus type A was found in 87 patients (77.6%), while influenza type B was present in only 25 (22.4%) patients. Out of the 15 non-survivors, 14 had influenza A. Only 17 patients (15.2%) were found to have positive culture of respiratory specimen, out of which 3 were non-survivors and 14 were survivors. Our analysis identified septic shock (odds ratio 45.24; 95%, confidence interval 6.20-330; p<0.001), renal failure (odds ratio 10.88; 95%, confidence interval 1.61-73.52; p=0.01) and ICU stay (odds ratio 17.22; 95%, confidence interval 2.68-110.5; p=0.003) as independent risk factors associated with in-hospital mortality.