Penicillin is the most commonly reported medication allergy. While up to 10% of patients report a history of penicillin allergy, more than 80% of these individuals lack penicillin-specific IgE antibodies. Penicillin skin testing is highly accurate in identifying who can safely receive the antibiotic at the time of testing, but its predictive value for future courses is unknown because it is uncertain whether patients with a history of penicillin allergy are at risk of becoming resensitized. To determine the rate of resensitization, 53 patients with negative penicillin skin test results and convincing histories of penicillin allergy were challenged over several months with 3 consecutive 10-day courses of oral penicillin. None of the patients who completed the protocol converted from a negative to a positive skin test result, yielding a resensitization rate of 0%. The results indicate that a negative penicillin skin test result is predictive for subsequent oral administration of penicillin beyond the time of testing.