<h3>Introduction</h3> Vaccine-associated anaphylaxis (VAA) is rare with an estimated 1.3 cases per 1 million doses administered. Though rare, VAA can cause vaccine hesitancy. Congenital heart disease patients are at greater risk for poor outcomes from vaccine-preventable infections; however, the use of beta-blockers and ACE inhibitors in these patients further complicates VAA testing and management. Such patients require prompt, careful risk-benefit analysis when formally evaluating VAA. <h3>Case Description</h3> We present a 17-year-old female with congenital Shone complex with post-operative complications resulting in moderate heart failure with reduced ejection fraction (HFrEF; EF <40%) who experienced VAA in 2009. The patient developed lip and facial swelling with cyanosis upon receiving influenza, MMR, VZV and DTaP/IPV vaccinations. She improved after two doses of intramuscular epinephrine. Referral for VAA evaluation was delayed until 2017, at which time her allergist performed serum bovine and porcine gelatin IgE (negative). Skin prick testing was negative but intradermal testing returned positive for the MenACWY-CRM (8mm/25mm) and Tdap (10mm/20mm) vaccines. Vaccine challenge was deferred. In 2022, her low EF and beta-blocker use warranted discussion with cardiology for risk-benefit analysis regarding vaccine and excipient skin testing and challenge. Vaccine titers were sent to guide skin testing, with plans to preemptively hold beta-blockers for 24-hours with inpatient challenge if testing returned negative. <h3>Discussion</h3> Beta-blockers improve clinical outcomes in HFrEF but can increase severity of anaphylaxis. Data regarding anaphylaxis in pediatric patients with HFrEF and beta-blocker use is limited, further necessitating multidisciplinary assessment of the short-term risks and long-term benefits when pursuing skin testing and challenge to vaccinations.