After Demon Spade betrayed the first generation Guardians, he later became Vongola Secondo's Mist Guardian through unknown circumstances. Their relationship with each other has not been shown, but Vongola Secondo was probably admired by Demon because his personality fit Demon Spade's ideal Vongola Boss. According to the Timoteo, the ways of the Vongola Famiglia began to change starting from Vongola Secondo's reign. When his reign ended, Vongola Secondo was succeeded by the unnamed Vongola Terzo.
He briefly appears in a flashback during the explanation of Xanxus's Flame of Wrath.
Vongola Secondo appears along with the rest of the previous Vongola Bosses when Tsunayoshi Sawada underwent the Vongola Trial. While Tsuna was trapped in ten-years-later Hibari's Porcospino Nuvola, the Sky Vongola Ring presented images of the past sins and crimes of the Vongola to his head. The previous bosses demanded Tsuna to accept the bloody history of the Vongola if he wanted to be strong, but Tsuna refused to do so as he would rather destroy the Vongola than accept their sins. Vongola Primo and the other bosses accepted Tsuna's resolve granted him the succession of the Vongola Famiglia. Tsuna's X-Gloves were then upgraded into the X-Gloves Version Vongola Ring as proof that he was given the Vongola inheritance.