To analyze the effects of 1 or more patient-reported allergies on clinical outcomes, in particular graft failure rate, and patient-reported outcomes (PROs) following osteochondral allograft transplantation (OCA) of the knee. Retrospective review of patients who underwent knee OCA from August 2010 to May 2021 with a minimum of 2-year follow-up. Patients were initially divided into 2 cohorts: those with at least 1 allergy and those without any allergies. Clinical outcomes assessed included graft failure, reoperation rates, deep vein thrombosis/pulmonary embolism, and manipulation under anesthesia/lysis of adhesions (MUA/LOA). PROs assessed, including the visual analog scale (VAS) for pain and satisfaction, the Knee injury and Osteoarthritis Outcome Score (KOOS), and return to sport rates, were compared. In total, 285 patients were included with a mean clinical follow-up of 4.8 ± 2.0 years. The allergy cohort had a significantly higher rate of graft failure (P= .008). In a regression analysis controlling for confounding variables, graft failure remained significantly associated with the presence of medication allergies (odds ratio [OR], 3.631; 95% CI, 1.139-11.577; P= .029). Furthermore, an increasing number of allergies were associated with an increased rate of graft failure (OR, 1.644; 95% CI, 1.074-2.515; P= .022). There was no difference in rate of reoperation, complications, infection, and MUA/LOA. Of the 100 patients who completed PROs, there was no difference in VAS satisfaction, pain, and any of the KOOS outcome scores or return to sport. The presence of 1 or more patient-reported allergies was shown to be significantly associated with OCA graft failure. Furthermore, an increasing number of patient-reported allergies were associated with a higher rate of graft failure. However, there were no significant differences in VAS satisfaction or pain, KOOS symptom, quality of life, pain, or return to sport in patients with at least 1 patient-reported allergy and those without allergies. Level III, retrospective cohort study.