The arrangements of 299 lasted until the mid-330s, when Shapur II begins a series of offensives against the Romans.

Despite a string of victories in battle, his campaigns achieve little lasting effect: three Persian sieges of Nisibis are repulsed, and while Shapur succeedsin taking Amida and Singara, both cities are soon regained by the Romans.

Following a lull during the 350s while Shapur fights off nomad attacks on Persia's northern frontier, he launches a new campaign in 359 and again captures Amida.

This provokes a major offensive in 363 by the Roman Emperor Julian, who advances down the Euphrates to Ctesiphon.

Julian wins the Battle of Ctesiphon but is unable to take the Persian capital and retreats along the Tigris.

Harried by the Persians, Julian is killed in a skirmish.

With the Roman army stuck on the eastern bank of the Euphrates, Julian's successor Jovian makes peace, agreeing to major concessions in exchange for safe passage out of Sassanid territory.

The Romans surrender their former possessions east of the Tigris, as well as Nisibis and Singara, and Shapur soon conquers Armenia.