Background: Chemotherapy (CHT) and monoclonal antibodies (mAbs) have been described as frequent causes of drug allergy. Currently, rapid drug desensitization (RDD) is a widely recognized and safe procedure extensively used to manage patients with drug hypersensitivity reactions (DHR). Nevertheless, despite its effectiveness, RDD can occasionally be hampered by severe breakthrough reactions (BTR) during the procedure, potentially leading to its failure.   Objective: Evaluate the usefulness and safety of adrenaline infusion (AI) as a coadjuvant during RDD in patients with severe DHR during standard desensitization protocols.      Methods: Retrospective observational study, analyzing data from patients who underwent RDD to CHT or mAbs in a tertiary hospital from January-2015 to January-2024. We included patients who required the use of AI to safely achieve RDD after a severe initial DHR or failure of standard RDD protocol due to repeated DHR. Comorbidities, adrenaline doses and adverse events (AE) were assessed.    Results: Forty-two patients met the inclusion criteria. Seventy-seven percent ( n=32) were women with a mean age of 57 years(range 32-83). Most frequent drugs involved in DHR were platinum-salts 58%, mAbs 26% and taxanes 14%. A total of 151 RDD were performed with coadjuvant AI. Skin tests were positive in 69% of patients. The most frequent initial BTR (65%, n=28) was moderate or severe anaphylaxis. The most common adverse events (AE) associated with AI were trembling and tachycardia (14% and 7% respectively). These symptoms subsided after reducing the AI infusion rate. The median cumulative dose of adrenaline administrated during the entire RDD procedure was 0.76µg(IQR 0.4-1.2µg SD 3.05), with a median infusion rate of 8ml/h(IQR 4-15ml/h), and median AI maximum rate of 3.33µg/min(IQR 2-5.3µg/min).       Conclusions: AI is a useful and safe therapeutic tool for selected high-risk desensitization procedures, contributing to mitigate severe DHR with mostly minor AE.