Kaloyan concluded an alliance with Theodore I Laskaris, Emperor of Nicaea. Laskaris had started a war against David Komnenos, Emperor of Trebizond, who was supported by the Latins. He persuaded Kaloyan to invade Thrace, forcing Henry to withdraw his troops from Asia Minor. Kaloyan laid siege to Adrianople in April 1207, using trebuchets, but the defenders resisted. A month later, the Cumans abandoned Kaloyan's camp, because they wanted to return to the Pontic steppes, which compelled Kaloyan to lift the siege. Innocent III urged Kaloyan to make peace with the Latins, but he did not obey.

Henry concluded a truce with Laskaris in July 1207. He also had a meeting with Boniface of Thessalonica, who acknowledged his suzerainty at Kypsela in Thrace. However, on his way back to Thessalonica, Boniface was ambushed and killed at Mosynopolis on 4 September. According to Geoffrey of Villehardouin local Bulgarians were the perpetrators and they sent Boniface's head to Kaloyan. Robert of Clari and Choniates recorded that Kaloyan had set up the ambush. Boniface was succeeded by his minor son, Demetrius. The child king's mother, Margaret of Hungary, took up the administration of the kingdom. Kaloyan hurried to Thessalonica and laid siege to the town. Kaloyan died during the siege of Thessalonica in October 1207, but the circumstances of his death are uncertain.