Background: Presentation of pandemic H1N1 influenza (H1N1) is widely evolving as it continues to involve different geographic locations and populations. This study was conducted to improve the precision of clinical diagnosis of H1N1 (2009) influenza infection in an outpatient setting. Materials and Methods: A prospective cross-sectional study was conducted among adult patients (age >15 years) with influenza-like illnesses (ILI) from November 2009 to February 2010. Clinical, laboratory and epidemiological findings in the first week of illness were collected using a standardized datasheet. Influenza testing was performed by real-time reversetranscriptase polymerase chain reaction (rRT-PCR). Results: Thirty nine (24%) patients were positive for H1N1 and 123 (76%) were negative for any subtype of influenza A virus. Whilst otalgia (14% vs. 0 p= 0.01) was more prevalent in non-influenza A cases, cough (90% vs. 72% p = 0.03) and shortness of breath (67% vs. 47% p = 0.02) were more often associated with H1N1-infection. Comparative analysis of coexisting conditions and demographic factors of patients revealed no other significant differences between the two groups. Conclusion: The clinical presentation of H1N1 (2009) infection is largely indistinguishable from other acute respiratory diseases. Although previous studies suggested significant differences in demographic and co-existing conditions of H1N1 infected patients, our study shows that as the pandemic spreads worldwide and affects the majority of the population, H1N1 diagnosis based on clinical presentation and demographic characteristics has become less practical and much more difficult in tertiary care centers. (Tanaffos2011; 10(2): 15-19)