Authorities say the 65-year-old became trapped in the third floor apartment on East 234th Street just after 12:50 a.m.
He was looking for his teenage daughter, but she was not at home. He was trapped by the flames and could not get out the front door. His wife climbed out the fire escape.
He was pronounced dead at Our Lady of Mercy Medical Center.
The wife was treated for a minor injury at Montefiore Medical Center.
A firefighter was also taken to the hospital.
The apartment was filled with bags and debris, an apparent fire hazard that may have fueled the flames.
The cause of the fire is under investigation.
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