He is particularly known for discovering Da Costa's syndrome (also known as soldier's heart), an anxiety disorder combining effort fatigue, dyspnea, a sighing respiration, palpitation and sweating that he first observed in soldiers in the American Civil War and documented in an 1871 study.

As a result of his childhood travel and international education, Da Costa originally wanted to enter the foreign service.

But let these facts be welded together by thought, their bearing traced by imagination, experiments devised by the mind projecting itself in advance of them, and the plodder is likely to become the great discoverer.

Jacob Da Costa worked at Satterlee General Hospital in Philadelphia during the American Civil War.

As a result of these studies, he identified a new condition he termed "irritable heart" (sometimes called Da Costa Syndrome) in 1862.