Introduction A drug allergy is an abnormal immune system reaction to a medication. Any medication can induce a drug allergy. However, a drug allergy is more likely with certain medicines, one of which is penicillin. The most common signs and symptoms of drug allergy are hives, rash, or fever. Up to 15.6% of patients self-reported having an allergy to penicillin, and most of those reported allergies lacked proper documentation (1). In addition, 90 percent of penicillin-allergic patients can tolerate penicillin and, therefore, are labeled unnecessarily (2,3). Using alternative broad-spectrum antibiotics in those patients prevents optimal medical care (1). Skin tests provide confirmatory evidence of sensitization to a given allergen. Therefore, the primary objective of this study is to estimate the prevalence of penicillin drug allergy by medical chart review and to identify the true drug-allergic patients. Methodology This is a retrospective observational study of the population by reviewing charts. The inclusion criteria were all patients labeled allergic to penicillin at KAMC between 1982 and December 2017. The second objective is a prospective interventional study of a skin prick and intradermal test (IDT) for penicillin allergy. We calculated the sample size, and the total required number of patients for the testing was 133. Results Of 2738 labeled allergic patients, 455 were labeled as penicillin allergy (16.6%). The majority were female participants, accounting for 338 (74.3%). Table 1 shows the baseline characteristics. Among all the participants, maculopapular rash was the most common documented symptom. Moreover, 18.7% (n=85) of the patients had either unknown or undocumented reactions. Penicillin drugs were classified into subgroups in which patients reacted. Penicillin (63.3%) was the most common, followed by Augmentin (15.8%), then amoxicillin (11.0%). Thirty participants (6.6%) received penicillin after they were labeled as allergic to penicillin and did not report any further reactions except for one participant who developed the rash. Conclusion As many as penicillin-labeled allergic patients, only a few are truly allergic to penicillin. This fact is attributed to poor documentation of allergies and based on the history taken from the patient that he might falsely relate a symptom or adverse effect to penicillin without being tested for penicillin allergy. This study recommends using proper documentation standards, such as penicillin skin tests when documenting patient allergies.