<h3>Introduction</h3> There is emerging data for safety and efficacy of graded challenges to penicillin (GCP), without penicillin skin testing, in patients with low risk reaction histories. We describe outcomes of GCP in ICU patients. <h3>Methods</h3> From 8/2021 to 6/2022, allergy/immunology physicians completed e-consults for ICU patients with a penicillin allergy label. Low risk history was defined as unknown reaction or a history of a cutaneous-only reaction >5 years ago and was verified by chart review or patient/family contact. GCP consisted of a 2-3 step challenge to amoxicillin or ampicillin. Patient demographics, GCP results, pre/post GCP antibiotics regimens, and a 2-4 week follow up were collected. <h3>Results</h3> There were 40 ICU patients with low-risk reaction histories. Historical reactions included: rash (17, 43%), hives (10, 25%), angioedema (5, 13%), and unknown (8, 20%). The median age was 63.5 years (interquartile range: 58.8- 72.3). Patient characteristics included: 24/40 patients (60%) intubated, 12/40 (30%) receiving steroids, 10/40 (25%) COVID-19+, 8/40 (20%) receiving vasopressors, 7/40 (18%) on antihistamines, and 1/40 (3%) on ECMO. A total of 32/40 (80%) patients underwent GCP. There was a negative GCP in 31/32 (97%) patients; one patient developed self-limited abdominal pain. Twelve of 32 (38%) patients transitioned to penicillins: from cephalosporins (10/12), vancomycin (3/12), metronidazole (1/12), meropenem (1/12), macrolide (1/12). There were 15/40 (37.5%) deaths at 2-4 weeks follow up. <h3>Conclusions</h3> : GCP was safe and efficacious in critically ill ICU patients with low risk reaction histories. Given the high ICU mortality, patients should be carefully identified for GCP.