A medical team completed the operation on Friday evening but said eight-week-old Rebeca Martinez had been susceptible to infection or haemorrhaging. The baby died 12 hours after the surgery, believed to be the first of its kind.
"She was too little to resist the surgery," the mother, 26-year-old Maria Gisela Hiciano, said by telephone from the hospital, sobbing softly.
She said doctors told her Rebeca died around 6 am on Saturday (10:00 GMT), seven hours after an operation that lasted more than 11 hours.
Dr Benjamin Rivera, one of two lead brain surgeons, said Rebeca had lost a lot of blood in the operation and had many transfusions, but that her blood would not clot.
"In that case, you can't do anything. This is the worst complication that can happen in this kind of surgery," Rivera told Associated Press.
The surgery had been successful in removing the second head, a partially formed twin that doctors said threatened the girl's development. It had its own partly developed brain, ears, eyes and lips.
During the surgery, 18 surgeons, nurses and doctors had taken several rotations to cut off the undeveloped tissue, clip the veins and arteries, and close the skull using a bone and skin graft from the second head.
Doctors had warned that Rebeca confronted "the second big risk, the post-operation recovery," according to Dr Santiago Hazim, medical director of Santo Domingo's Centre for Orthopaedic Specialties, where the surgery was performed.
The operation was critical because the head on top was growing faster than the lower one, said Dr Jorge Lazareff, the lead brain surgeon and director of paediatric neurosurgery at the University of California at Los Angeles' Mattel Children's Hospital.
Without an operation "the child would barely be able to lift her head at three months old," Lazareff said before the operation. He led a team that successfully separated conjoined Guatemalan twin girls in 2002.
Hiciano and her husband, 29-year-old Franklin Martinez, have two other children, aged four and one.