A former stage actor, he appeared in many motion pictures produced by Kalem Company and later moved to directing, becoming one of the silent screen's most prolific directors.

[9] In 1907 he joined Kalem Studios, starring in numerous movies directed by his long-time friend Sidney Olcott often dealing with Irish culture such as The Lad from Old Ireland (1910), The Colleen Bawn (1911), and Arrah-na-Pogue (1911).

The Kalem Company traveled across Europe and Middle East, where Vignola did one of his most notable roles as Judas Iscariot in From the Manger to the Cross (1912), among the most acclaimed films of the silent years.

The Vampire (1913), starring Alice Hollister, was well received by critics and is sometimes cited as the earliest surviving "vamp" movie (another title with the same name produced by William Nicholas Selig in 1910 is considered lost).

[11] He returned to the theme with The Vampire's Trail (1914), featuring Alice Joyce, Tom Moore and Hollister in a secondary role.

He had a long association directing the early movies of Pauline Frederick such as Audrey (1916), Double Crossed (1917), and The Love That Lives (1917).

[12] In 1920, he was offered the role of director-general for the Kinkikan Cinematograph Company in Japan[13] and was honored as "outstanding director of the year" by Frederick James Smith of the Motion Picture Classic in 1921.

[18] Sidney Olcott, alone after the passing of his wife Valentine Grant, spent his later life at Vignola's home, where he died in 1949.

[7] Vignola visited his birthplace Trivigno with his family, provided money to build the town's war monument and maintained correspondence with some of his relatives.