TTTS usually develops in mid-pregnancy from about 16 weeks to about 28 weeks. The mother generally notices that her abdomen rapidly increases in size, sometimes even larger than a full term pregnancy.
The mother may also experience tightening, lower abdominal pain, lower backache, and swollen feet and ankles. If left untreated the large amount of amniotic fluid can cause ruptured membranes or preterm labour. Untreated, very few twins survive TTTS.

This condition can also lead to the death of one of the twins before delivery. If one monochorionic twin dies before delivery the vascular connections in the placenta can cause significant risk to the co-twin. During the moments around death the fall of blood pressure in the dying twin causes further acute transfusion from the co-twin. In about half of these cases the transfusion is very small and the co-twin can survive and remain well. In about a quarter of these cases the co-twin loses so much blood that it also dies. In the remaining quarter the co-twin survives, but can sustain major damage to the brain and other organs because of the acute loss of blood. Long term major disabilities such as cerebral palsy and major developmental delay may occur.

Brain injury can also occur in TTTS even when both twins survive. Few studies, however, have reported on long-term neurodevelopmental outcome.