The aim of the present study was to assess the effect of a congenital Schistosoma japonicum infection on the establishment, fecundity, and pathogenicity of a postnatal challenge infection. Five prenatally S. japonicum–infected piglets received a challenge infection (prenatal challenge group), 5 prenatally infected piglets were followed without challenge (prenatal group), and 10 piglets, born by unexposed sows, served as challenge controls (challenge control group). Challenge infections were given 8 wk after the piglets were born (14 wk after the primary infection of the sows), and the study lasted another 11 wk. Variables included worm burden, tissue egg count, and liver pathology. Worm establishment and tissue egg count were comparable in the prenatal challenge group and in the challenge control group, both exceeding at a statistically significant level those in the prenatal group. No difference in worm fecundity (eggs/female worms/g tissue) was seen between the 3 groups. Liver pathology (i.e., portal and septal fibrosis) was more severe in the challenge control group compared to the other groups. A congenital S. japonicum infection in piglets thus affected neither establishment nor fecundity of a postnatal challenge infection. In spite of this, the challenge infection gave rise to much less liver pathology than the similarly sized challenge control infection.