He is known for formulating Osthoff's law, and published widely on Indo-European word-formation and morphology.

Shortly afterwards, he was granted full professorship at Heidelberg, where he later served as dean (1894/95) and vice-rector (1899–1900).

Along with Karl Brugmann and August Leskien, he was a significant figure in the founding of the Neogrammarians.

[1] He was a vocal critic of a young Ferdinand de Saussure's pioneering work Mémoire sur le système primitif des voyelles dans les langues indo-européennes, in which the 20-year-old Saussure postulated the laryngeal theory in 1879.

However, Saussure's theory was confirmed with the discovery of Hittite in the early 20th century.