Aim: To determine the effectiveness of prenatal treatment for clinical manifestations of congenital toxoplasmosis. Methods: We prospectively identified 255 live-born infants with congenital toxoplasmosis using prenatal or neonatal screening. We determined the effect of prenatal treatment on the risks of intracranial or ocular lesions in infancy, accounting for gestational age at maternal seroconversion. Results: Prenatal treatment within 4 wk of seroconversion reduced the risk of intracranial lesions compared with no treatment (odds ratio, OR 0.28; 95%CI: 0.08-0.75), but there was no significant effect when initiated after 4 wk (OR 0.76; 95%CI: 0.35-1.59; overall p-value 0.19). Compared to spiramycin alone, no treatment doubled the risk of intracranial lesions (OR 2.33; 95%CI: 1.04-5.50), but the risk did not differ with pyrimethamine-sulp-honamide treatment (overall p-value 0.52). There was no consistent relationship between the type or timing of treatment and the risk of ocular lesions. Gestational age at maternal seroconversion was inversely associated with the risk of intracranial but not ocular lesions. Conclusion: Only early versus no prenatal treatment for intracranial lesions showed a statistically significant benefit. A large randomized controlled trial andor meta-analysis of individual patient data from cohort studies is required to confirm these findings. Aim: To determine the effectiveness of prenatal treatment for clinical manifestations of congenital toxoplasmosis. Methods: We prospectively identified 255 live-born infants with congenital toxoplasmosis using prenatal or neonatal screening. We determined the effect of prenatal treatment on the risks of intracranial or ocular lesions in infancy, accounting for gestational age at maternal seroconversion. Results: Prenatal treatment within 4 weeks of seroconversion reduced the risk of intracranial lesions compared with no treatment (odds ratio, OR 0.28; 95% CI: 0.08-0.75), but there was no Significant effect when initiated after 4 wk (OR 0.76; 95% CI: 0.35-1.59; overall p-value 0.19). Compared to spiramycin alone, no treatment doubled the risk of intracranial lesions (OR 2.33; 95% CI: 1.04-5.50 ), but the risk did not differ with pyrimethamine-sulp-honamide treatment (overall p-value 0.52). There was no consistent relationship between the type or timing of treatment and the risk of ocular lesio ns. Gestational age at maternal seroconversion was inversely associated with the risk of intracranial but not ocular lesions. Conclusion: Only early versus no prenatal treatment for intracranial lesions showed a significant benefit. A large randomized controlled trial and or meta-analysis of individual patient data from cohort studies is required to confirm these findings.