Background: Human Cytomegalovirus (HCMV) is the main cause of congenital infections in industrialized countries, with incidence ranging between 0.3 and 2.4%. Complications of congenital HCMV infection may include deafness and mental retardation. Primary HCMV infection during pregnancy carries a high risk of vertical transmission. An uncontrolled, non-randomized study published in 2005 reported that the intravenous administration of anti-CMV immunoglobulin (Ig) reduced the maternal–fetal transmission of the virus from 40 to 16%. Design and population: This is an experimental non-randomized spontaneous monocentric study — Phase 2. Material and methods: Between 2003 and 2007: 26 pregnant women with primary CMV infection documented serologically and/or virologically between the 6th and 22nd weeks of pregnancy were enrolled to receive anti-CMV IgG (Cytotect) monthly from the moment of diagnosis until birth. Results: Children born to 15 mothers (57.96%) were uninfected, while the newborns of 8 mothers (30.76%) presented CMV infection; 2 of these were symptomatic (1 with hearing impairment, 1 with encephalopathy), while the third, although asymptomatic, showed neuroradiological alterations. The remaining 3 pregnancies were interrupted by miscarriage in 1 case and voluntary abortion in 2 cases because of signs of CMV infection-induced alterations on ultrasonography. Overall, 42.3% of newborns/fetuses were infected. None of the expecting mothers presented side effects. Conclusions: Our study revealed no advantage in the use of anti-CMV IgG. Nevertheless, controlled, and ideally, randomized trials are warranted to better clarify the usefulness of this therapeutic approach.