Portinari was an employee in the Bruges branch for a very long time, more than 25 years, but never rose higher than assistant manager and factor, apparently at the insistence of Cosimo de' Medici, who did not trust him.
When Francesco Sassetti's influence removed the long-standing ban on lending to secular officials in 1471, Portinari used his position to make very large and extremely risky unsecured loans to Charles the Bold—loans which were never repaid and cost the bank heavily.
He may also have commissioned The Last Judgment, by Hans Memling, as it has been suggested that the soul of the sinner being weighed on the scales of St. Michael is in fact a donor portrait of Portinari.
This painting, also intended for a Florentine church, was hijacked by pirates from the Baltic Sea, leading incidentally to a lengthy lawsuit against the Hanseatic League to force them to return it.
His attempts to start his own bank failed, his past services to the Medici and the Duchy of Burgundy were forgotten, and he died a pauper in the Hospital of Santa Maria Nuova, which his ancestor Folco di Ricovero Portinari had founded in 1288.