BACKGROUND: A gap in the literature exists regarding the association between number of allergies and patient-reported outcomes measures (PROMs) for patients undergoing spine surgery. METHODS: Consecutive cervical or lumbar spine surgery patients were identified from a prospective registry from April 2017 to July 2020. Patients were grouped into those with 0, 1, 2, or ≥3 allergies. Demographics were compared between the groups. PROMs included Neck Disability Index, Oswestry Disability Index, visual analog scale (VAS) neck pain, VAS arm pain, VAS back pain, VAS leg pain, short form 12 (SF-12) physical component score, SF-12 mental component score, and patient-reported outcomes measurement information system physical function (PROMIS-PF), and outcomes were compared between the groups through multivariable analysis at up to 1-year follow-up. Associations between number of allergies and achieving a minimal clinically important difference (MCID) in the 9 aforementioned PROMs at 1-year follow-up were assessed. RESULTS: This study included 148 cervical and 517 lumbar patients. After controlling for demographic differences, a higher number of allergies was associated with less improvement in VAS neck pain, SF-12 physical component score, and PROMIS-PF at 12 weeks following cervical surgery and less improvement in PROMIS-PF at 2 weeks following lumbar surgery ( < 0.05). However, these associations failed to persist after 6 months and 12 weeks following surgery in cervical and lumbar patients, respectively ( > 0.05). No association was identified between number of allergies and achievement of MCID in any of the 9 studied PROMs at 1-year follow-up. CONCLUSIONS: The higher number of allergies was associated with less improvement in PROMs in the early postoperative period but not at longer-term follow-up. CLINICAL RELEVANCE: These findings provide data that can be utilized while counseling patients and setting postoperative expectations.