This study prospectively documents the incidence of penile inflammation in a consecutive sample of boys according to circumcision status whose visit with the physician included a genital examination in a private primary care pediatric practice in rural northern Wisconsin. Penile inflammation was more common in circumcised than noncircumcised boys, especially in the first 3 years of life (exact odds ratio, 8.01, 95% confidence interval, 31-329.15). When adjusted for the number of genital examinations and age younger than 3 years, exact logistic regression found an adjusted exact odds ratio of 7.91 (95% confidence interval, 1.76-77.66). The study found that rather than protecting against penile inflammation, neonatal circumcision increases the risk of penile inflammation, particularly in boys younger than 3 years old.