On 10 March 1855, around eight at night, a second calamitous fire struck the College. Despite the attempts by Latrobe to fireproof the building a half-century earlier, Nassau Hall was again gutted.

John Maclean Jr. , Class of 1816, now President, gave a full report to the Trustees at an emergency meeting a fortnight after the blaze. It was an accident, he told the Trustees; a piece of burning coal had landed on a carpet in a second-floor dormitory room. The occupant of the room was at Maclean's house when his room went up in flames.

Maclean noted that although the portraits in the southern pavilion had been saved, many students had lost all their possessions. He described a variety of actions taken to clear the rubble, collect the College's insurance, and shut down the refectory, now that students were boarding off campus. He also mentioned discussions with John Notman of Philadelphia, who had been brought to Princeton to "examine the walls and furnish some estimates."

A student's contemporary account of the fire