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In episode 5 of Despair Arc, Mikan nurses Ryota back to health after the Ultimate Imposter brought her to his room, being worried about his friend who was overworking on his anime and neglecting his health. Tsumiki is thankful for being trusted with the secret about the Ultimate Imposter taking Ryota's identity at school so that Mitarai could focus on creating his anime, and never shares it with anyone. Mikan has been checking on Ryota's health along with the Imposter ever since.
In episode 7, the Imposter informs Mikan about Ryota's disappearance. Tsumiki then goes to Mitarai's room to search for him, only to find and be kidnapped by Mukuro Ikusaba. The Ultimate Soldier brings her to Ryota's new room that was "borrowed" from one of the trustees by Junko Enoshima. Mikan and Ryota are glad that each other is alright and Junko suggests to watch Ryota's anime to celebrate their reunion. Mikan is moved to tears after watching it. Going to meet with Izuru Kamukura, Junko and Mukuro leave the two together and Junko tells Ryota he can use Mikan's breasts as pillows.
In episode 8, Ryota notices Mikan's strange behavior after seeing she's madly in love with Junko. He then finds a test version of Junko's despair anime on his computer. After watching it, a brainwashed Mikan attempts to have sex with him while asking him to join her and Junko in spreading despair. Her attempt is however interrupted with Junko's return, who then explains how her brainwashing anime works to the Ultimate Animator and threatens him to help her develop it further. While trying to run away, Ryota is caught by a brainwashed Mikan.
In Hope Arc, Mikan tells Ryota to join her and their classmates in atoning for their sins. Although the two don't interact, with Ryota knowing the techniques of Junko's brainwashing anime, Mikan being restored to her original self, Ryota being forgiven for his unintentional part in the Tragedy and the Class going to Jabberwock Island together, it can be assumed that Ryota has forgiven Mikan her attempt at raping him and the two restored their old friendship.
In Danganronpa V3's bonus mode, Ultimate Talent Development Plan, there is an event where Ultimate Imposter brings Hifumi Yamada to Mikan after the Ultimate Fanfic Creator has been overworking on his doujins. Imposter comments he had Mikan help his friend in a similar situation, referencing Ryota Mitarai, which means that Mikan and Ryota's friendship in the universe of this bonus mode is similar to the one from Despair Arc.
- “Oh, we can't do this? What can't we do? Do you mean "that"? Or... Do you mean "this"--?”
- — Despair Mikan trying to seduce Ryota in the subbed version of Episode 8 of Despair Arc.
While Danganronpa 3: The End of Hope's Peak Academy is highly criticized, the friendship between the Ryota Mitarai and Mikan Tsumiki is one of the most well-received parts about it. The ship is quite popular for the "Ill Boy and Medic Girl" dynamics that they share with Komamiki.
In spite of this, it is often overlooked by the fans. Some have also abandoned the ship after Mikan tried to rape Ryota after being brainwashed. While the ship still remains as one of the most popular shipping choices for Ryota, its popularity is greatly overshadowed by some of Mikan's more popular ships, namely Hinamiki and Komamiki.
Some fans are not able to choose between this ship and both characters' ships with the Ultimate Imposter, Mitworai and Twomiki, or enjoy the dynamics between all three of them, resulting in Mitwomiki.
- Mikan's relationship with Ryota on Danganronpa Wiki
- Ryota's relationship with Mikan on Danganronpa Wiki