In 1911-12 he returned to Switzerland and joined the Swiss Geodetic Commission. In 1913, he arranged with Schlesinger to come to Allegheny Observatory as his assistant, but World War I interrupted his plans and he was ,obilized and stationed in the Alps by Swiss army.
In spring 1915, on intervention of Schlesinger, he was released and permitted to travel to the US, and in May 1915 started to work as astronomer at the Allegheny Observatory. There, he started his investigations of star clusters.
In 1918, he went to Lick Observatory to work with W.W. Campbell. In 1922, he took part in an expedition to observe the Solar Eclipse of September 21 in Wallal, Australia, in order to test Einstein's then-new Theory of General Relativity. He carefully observed and studied planet Mars during its oppositions in 1924 and 1926.
In the following years, Trumpler made his most significant discovery and contribution to astronomy, namely his investigation of distances, dimensions, and space distribution of galactic open star clusters (Trumpler 1930); this work also contains a table of 37 new open clusters, now known as the Trumpler catalog. Moreover, from these studies, Trumpler discovered the interstellar extinction; this effect has significant impact on distance estimates and considerable effect on the distance scale of the Milky Way and the universe.
In 1938, Trumpler changed from Lick to the Berkeley Astronomy department, and in 1951 retired to Rio del Mar, California. On September 10, 1956 he died after a few days in hospital in Oakland, California.