A surgeon and obstetrician-gynecologist, Cole was among the first to perform some of the newer surgical procedures of his era, such as the Caesarean section and ligation of the common carotid and femoral arteries.

At one point, a decision was made to insert a sponge into King's chest, and this approach was supported by prominent surgeon Hugh Toland.

Cole disagreed with the decision and provided testimony to that effect when the San Francisco Committee of Vigilance called for an investigation into the man's medical care after his death.

The school closed within two years, and Cole spent most of the American Civil War period in Europe, where he toured hospitals in several countries.

When he returned to the US in 1865, most of the former University of the Pacific faculty members were working at Toland Medical College, which had been established by Cole's rival.

Cole assisted in the negotiations when Toland Medical College merged with the state's public university system in 1873.