[1] He returned in 1880 to San Francisco, which at the time was a fairly provincial Western town despite its wealth, with buildings designed in a variety of architectural styles.

[1] In 1882, Pissis became a member of the American Institute of Architects (AIA) and, with his partner William P. Moore, designed a number of buildings in flamboyant Queen Anne and Eastlake styles.

[1] However, by the 1890s he was a major figure in the Neoclassical (Classical Revival) movement, particularly Beaux-Arts, and introduced that style to San Francisco beginning with the Hibernia Bank building in 1892.

[2] Pissis played a major role in San Francisco's reconstruction following the Great Earthquake of 1906, both as a designer of a number of the city's landmark buildings,[2] and as a member of the Committee of Fifty.

Although popular and internationally known at the time, Pissis's approach to design was derided by later critics as reactionary, and blamed for suppressing more original architects such as Frank Lloyd Wright and Louis Sullivan in favor of imitation of older European traditions.