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Fourth war (1512–1522)

Despite the peace treaty, the relationship between the two countries remained tense. Sigismund I demanded Michael Glinski's extradition 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 Order 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 (1519–1521) and allied Maximilian I, Holy Roman Emperor with Vasili III.

In December 1512, Moscow invaded the Grand Duchy of Lithuania seeking 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.

Russia then suffered a series of defeats in the field. In 1512, Grand Hetman of Lithuania, Konstanty Ostrogski, ravaged Severia and defeated a 6,000-strong Russian force. On 8 September 1514, the Russians suffered a major defeat at the Battle of Orsha. Despite their victory, his army was unable to move quickly enough to recapture Smolensk. In 1518, Russian forces were beaten during the siege of Polotsk, when according to 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. Khan of Crimea, Mehmed I Giray 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 the attack and tried to take Ryazan.

In 1522, a treaty was signed that called for a five-year truce, no prisoner exchange, and for Russia to retain control of Smolensk. The truce was subsequently extended to 1534.