Abstract Background The label of penicillin allergy is carried by between 8 and 25% of all patients (1). Alternative antibiotics may not be as efficacious, can be more expensive and lead to more adverse effects (2). Interrogation of a penicillin allergy is an important stewardship intervention considering only 1-10% of these patients are truly allergic to penicillin (1). The aim of this study was to investigate if a penicillin allergy de-labelling project altered antibiotics subsequently prescribed in a hospital setting. Methods A review was carried out of 75 patients identified as part of a penicillin allergy de-labelling project in Galway University Hospital over a 15 month period. Self-reported penicillin allergy by hospitalized patients was investigated and clarified by a collaboration from pharmacy, immunology and infectious diseases. Allergy labels were either reinforced, immediately de-labelled or further investigated with skin testing or oral challenge. Antibiotics prescribed prior to allergy de-labelling and following allergy clarification were noted. This information was obtained from the electronic hospital record. Results In total, 118 patients had penicillin allergy assessment. 75 patients had their penicillin allergy de-labelled. 44 patients were de-labelled from history, 22 were de-labelled after skin testing and oral challenge and 9 were de-labelled following an oral challenge only. 47 patients (63%) received penicillin post de-labelling. Out of these 47 patients, 27 had been previously treated with fluoroquinolones (57%), 4 had received teicoplanin surgical prophylaxis for surgical procedures (9%), 4 had received linezolid, 2 had received ceftazidime and 2 had been seemingly prescribed meropenem based on allergy. Conclusions These results demonstrate that appropriate de-labelling of penicillin allergy has a positive impact on future antibiotic prescription in a hospital setting. It results in reduced use of fluoroquinolones as well as other restricted antibiotics with higher risk of adverse effects and is a useful antimicrobial stewardship tool.