A professional painter and engraver by age seventeen, Sirani opened her own studio in Bologna early in her career, supported chiefly by private commissions. She was so prodigious an artistthat by the time of her death at 27, she had completed approximately 170 paintings, 14 etchings, and a number of drawings. In 17th century Bologna, which boasted such well known women artists as Properzia de' Rossi and Lavinia Fontana, Elisabetta Sirani was considered a virtuoso. Several stories attest to Sirani's rapid working methods, such as when the Grand Duke Cosimo III de Medici visited her studio in 1664. After he watched her work on a portrait of his uncle Prince Leopold, he ordered a Madonna for himself, which Sirani allegedly executed quickly so that it could dry and be taken home with him.

Elisabetta was taught by her father, Giovanni Andrea Sirani, one of Guido Reni's pupils and later his principal assistant. According to Fiorella Frisoni, author of the essay on Sirani in Italian Women Artists from Renaissance to Baroque, because of the success of her early paintings, both large altarpieces, such as the canvas she painted for the Church of San Gerolamo della Certosa in 1658, and small-scale paintings of the Madonna and Child or the Holy Family that she began painting around 1660, Sirani "became known as a virtuosa, to be shown off to distinguished foreigners passing through Bologna, who did not fail to pay a visit to her studio" and patronized by aristocratic patrons, including members of the Farnese and Medici families, for whom she produced works including female saints or heroines like Judith or Portia. At her untimely death, she was called "the glory of the female sex, the gem of Italy, and the sun of Europe" by Carlo Malvasia, her patron and first biographer in Felsina pitrice. In addition to her paintings, she was a fluent draftsman and a distinguished etcher.

Below are just a few of Elisabetta Sirani's Prints:

'Painter-Etcher' 1638-1665

'Unknown' 1638–1665; etching

'St. Eustace'. Original etching, 1655.