BACKGROUND: We studied women and their infants to evaluate risk factors for congenital transmission and cardiomyopathy in Trypanosoma cruzi-infected women. METHODS: Women provided data and blood for serology and quantitative polymerase chain reaction (PCR). Infants of infected women had blood tested at 0 and 1 month by microscopy, PCR and immunoblot, and serology at 6 and 9 months. Women underwent electrocardiography (ECG). RESULTS: Of 1696 women, 456 (26.9%) were infected; 31 (6.8%) transmitted T. cruzi to their infants. Women who transmitted had higher parasite loads than those who did not (median, 62.0 [interquartile range {IQR}, 25.8-204.8] vs 0.05 [IQR, 0-29.6]; P < .0001). Transmission was higher in twin than in singleton births (27.3% vs 6.4%; P = .04). Women who had not lived in infested houses transmitted more frequently (9.7% vs 4.6%; P = .04), were more likely to have positive results by PCR (65.5% vs 33.9%; P < .001), and had higher parasite loads than those who had lived in infested houses (median, 25.8 [IQR, 0-64.1] vs 0 [IQR, 0-12.3]; P < .001). Of 302 infected women, 28 (9.3%) had ECG abnormalities consistent with Chagas cardiomyopathy; risk was higher for older women (odds ratio [OR], 1.06 [95% confidence interval {CI}, 1.01-1.12] per year) and those with vector exposure (OR, 3.7 [95% CI, 1.4-10.2]). We observed a strong dose-response relationship between ECG abnormalities and reported years of living in an infested house. CONCLUSIONS: We hypothesize that repeated vector-borne infection sustains antigen exposure and the consequent inflammatory response at a higher chronic level, increasing cardiac morbidity, but possibly enabling exposed women to control parasitemia in the face of pregnancy-induced Th2 polarization.