Firefighters were called to a property at Brooke Drive, off Blacks Road in the early hours of Wednesday morning.
The man and his brother managed to escape the first floor fire at around 2am before fire appliances arrived, however, their sister was trapped upstairs.
Crews managed to rescued the woman, who is in her 70s, by ladder. She is in a stable condition in hospital.
The other brother underwent surgery on Wednesday afternoon.
NI Fire and Rescue Service said the mid-terrace house was well alight on arrival.
"All occupants were taken to hospital, via ambulance," the statement read.
Geraldine Clifford, a neighbour, said she awoke to a dramatic scene overnight.
"I just saw the thick black smoke coming out the windows," she told UTV. "There were fire engines and ambulances outside and they had the whole street blocked off.
"They are quiet people, they've been beside me 40 years this year and they're good neighbours, if I ever needed help they're always there."
An investigation is now underway to establish the cause of the fire.
A police spokesperson said that the blaze is not believed to be malicious at this stage.