Up to 11% of patients report a penicillin allergy (PA), with 1-2% demonstrating a true IgE mediated allergy upon testing. PA patients often receive non-beta-lactam antibiotic surgical prophylaxis (non-BLP). This study evaluates the relationship of PA to outcomes after open ventral hernia repair (OVHR). A prospective institutional database was queried for patients undergoing OVHR. Demographics, operative characteristics, and outcomes were evaluated by the reported PA and the administration of beta-lactam prophylaxis (BLP). Allergy histories were reviewed in 1178 patients. PA was reported in 21.6% of patients, with 55.5% reporting rash or hives, 15.0% airway compromise or anaphylaxis, and 29.5% no specific reaction. BLP was administered to 76.3% of patients, including 22.1% of PA patients and 89.9% of patients without PA. PA patients were more often female (64.6% PA patients vs. 56% non-PA, p = 0.01), with higher rates of chronic steroids, MRSA, anxiety, asthma, COPD, chronic pain, and sleep apnea (p < 0.03 all values). PA patients had higher rates of contaminated cases, including mesh infection and fistula. Of the 683 clean cases, 82.1% received BLP. Of the 117 clean contaminated cases (CDC wound class 2), 82.9% received BLP, which was associated with reduced long-term readmission for hernia complications (21.5 vs. 55%, p = 0.002, OR 0.27, CI 0.09-0.83). In the 120 CDC wound class 3 and 4 patients, 65.8% received BLP. In multivariate analysis, BLP was associated with lower rates of reoperation (OR 0.31, CI 0.12-0.76) and recurrence (OR 0.32, CI 0.11-0.86). BLP was given to 22.1% of the PA patients with no adverse reactions noted. PA patients had more comorbidities and complex ventral hernias. When controlling for contamination and MRSA history, BLP is associated with improved outcomes particularly in contaminated cases. PA may be a risk factor for patient complexity, and further studies are warranted to determine if allergy testing can be warranted in known or anticipated contaminated cases.