Despite the peace treaty, the relationship between two countries remained tense. Sigismund I demanded that Moscow would turn in Michael Glinski for trial, while Vasili III demanded better treatment of his widowed sister Helena. Vasili also discovered that Sigismund was paying Khan Meñli I Giray to attack the Grand Duchy of Moscow. At the same time, Albert of Prussia became the Grand Master of the Teutonic Knights and was unwilling to acknowledge Poland's suzerainty as required by the Second Peace of Thorn (1466). The tension eventually resulted in the Polish–Teutonic War (1519–21) and allied Maximilian I, Holy Roman Emperor with Vasili III.
In December 1512, the Muscovy invaded the Grand Duchy of Lithuania with a goal to capture Smolensk, a major trading center. Their first six- and four-week sieges in 1513 failed, but the city fell in July 1514. Prince Vasily Nemoy Shuysky was left as viceregent in Smolensk. This angered Glinski, who threatened to rejoin Sigismund I, but was imprisoned by the Russians.
Thereupon, Russia suffered a series of defeats in the field; first, in 1512, Grand Hetman of Lithuania, Konstanty Ostrogski, ravaged Severia and defeated a 6,000-strong Russian force, and, in 1514, after taking Smolensk again, the Russians suffered a major defeat at the Battle of Orsha (on 8 September).
Despite their victory the Polish–Lithuanian army was unable to move quickly enough to recapture Smolensk. In 1518, Russian forces were beaten during the siege of Polotsk, when according to the legend the Lithuanian forces were inspired by the sight of their patron saint, Saint Casimir. The Russians invaded Lithuania again in 1519 raiding Orsha, Mogilev, Minsk, Vitebsk and Polotsk.
By 1521, Sigismund had defeated the grand master and allied with the Kazan and Crimean Tatar hordes against Moscow. In 1521, the Crimean khan Mohammed-Girey carried out a ruinous attack on the Moscow principality, resulting in a commitment from the grand prince to pay tribute. The Lithuanian troops led by Dashkovich participated in it and tried to take Ryazan.
In 1522 a treaty was signed which called for a five-year truce, no prisoner exchange, and Russia to retain control of Smolensk. The truce was subsequently extended to 1534.