The 1981 Italian Open was a combined men's and women's tennis tournament that was played on outdoor clay courts.

For the second time in the history of the tournament the men and women competed in different locations.

The men's event was held at the traditional location of Foro Italico in Rome, while the women played in Perugia.

Third-seeded José Luis Clerc won the men's singles title and the accompanying $24,000 first-prize money.

[4] José Luis Clerc defeated Víctor Pecci 6–3, 6–4, 6–0 Chris Evert-Lloyd defeated Virginia Ruzici 6–1, 6–2 Hans Gildemeister / Andrés Gómez defeated Bruce Manson / Tomáš Šmíd 7–6, 7–6 Candy Reynolds / Paula Smith defeated Chris Evert-Lloyd / Virginia Ruzici 7–5, 6–1