Though the suppression of this rebellion quelled all serious threats to Tokugawa rule, it was nonetheless an unsure era.

Parents Adopted daughter: Tokugawa Iemitsu died in early 1651, at the age of forty-seven.

[2] Until he came of age, five regents were to rule in his place, but Shogun Ietsuna nevertheless assumed a role as formal head of the bakufu bureaucracy.

During the reign of Shogun Iemitsu, two samurai, Yui Shōsetsu and Marubashi Chūya, had been planning an uprising in which the city of Edo would be burned to the ground and, amidst the confusion, Edo Castle would be raided and the shōgun, other members of the Tokugawa and high officials would be executed.

Nonetheless, the plan was discovered after the death of Iemitsu, and Ietsuna's regents were brutal in suppressing the rebellion, which came to be known as the Keian Uprising or the "Tosa Conspiracy".

In Meireki 3 (1657), on the 18th–19th days of the 1st month, when Ietsuna was almost 20 years old, a great fire broke out in Edo and burned the city to the ground.

It is said that his relationship was quite good with Asa no Miya, though they didn't have a child; they adopted Naohime, daughter of Tokugawa Mitsutomo.

In some cases, however, Ietsuna acted upon his own accord, as when he came up with the idea of abolishing junshi, where a samurai follows his lord into death.

Following the succession dispute of the Date, very few disturbances occurred for the remainder of Ietsuna's reign, except some defiant daimyōs.

In 1679, shōgun Ietsuna fell ill. His succession began to be discussed, in which Sakai Tadakiyo took an active role.