Background:The first-line method in the diagnosis of patients who describe an immediate reaction after penicillin intake is skin tests(ST)with penicillin reagents. We aimed to determine the safety and diagnostic value of penicillin STs in the diagnosis of immediate reactions to penicillins. Methods:The study included patients with suspected immediate reaction to penicillin who were subjected to STs using a standard penicillin test kit (Diater;Madrid,Spain) and suspected penicillin and drug provocation tests(DPT) with suspected penicillin at our clinic Results:A total of 191 patients(53.9%males)with a median age of 6.83 years(inter-quartile range:4.2-12)were included in the study.The time from drug intake to the onset of reaction was ≤1 hour in 138(72.3%)patients and 1 to 6 hours in 53(27.7%)patients.Penicillin allergy was confirmed by diagnostic tests in 36(18.8%)of 191 patients.In multivariate logistic regression analysis, history of both urticaria and angioedema(odds ratio[OR]:27,683 95%confidence interval[CI]:3.143-243.837,p = 0.003) and anaphylaxis (OR:56.246, 95%CI:6.598-479.489, p <0.001) were main predictors of penicillin allergy diagnosis. While STs were positive in 23(63.8%)patients, 13(26.2%)patients had positive DPT results despite negative ST results. The negative predictive value(NPV)of STs was calculated 92.2% (155/168).None of our patients experienced immediate or delayed systemic/local reactions in relation to the STs. Conclusions:History of urticaria with and anaphylaxis were main predictors of true penicillin allergy in children with suspected immediate reactions.Skin tests with penicillin reagents are safe for use in children. Although STs have a high NPV, DPT is the gold standard for diagnosis. Drug provocation tests should be performed as the final step of the diagnostic evaluation of penicillin allergy in patients with negative STs