Background: Penicillin (PCN) accounts for most cases of antibiotic allergies. Reported PCN allergy deprives the patient from this class of antibiotics and creates hesitancy in using other beta-lactam antibiotics. The aim of this study is to report the prevalence of self-reported PCN allergy among adult patients admitted to the hospital and to examine the probable validity of these reports. Methods: A questionnaire was conducted among 192 patients with self-reported PCN allergy who were admitted to a community hospital between July 25, 2011 and January 25, 2012. Patients admitted with an infection and treated with a beta-lactam were also followed until hospital discharge. Results: The mean age of patients at the time of their self-reported allergic reaction was 20.3 years. The most common allergic symptoms reported in decreasing order of frequency were itchy rash, angioedema, and urticaria. Based on analysis of the questionnaires, 121 patients (63.0%) had probable PCN allergy, 54 (28.1%) had possible PCN allergy, and 17 (8.9%) were unlikely to have a PCN allergy. Fifty-one participants (26.6%) had self-reported subsequent exposure to PCN in their life. This subsequent exposure was well tolerated in 86.3% of the participants. Fifty participants (25.9%) had self-reported subsequent exposure to a first generation cephalosporin and it was well tolerated in 78.4% of them. Conclusion: Taking a detailed history from patients with self-reported PCN allergy can help to distinguish a true PCN allergy from a false positive report of allergy and hence allow clinicians to use this important class of antibiotics when truly indicated. © 2013 Khasawneh et al.