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Set in Japan predominantly during the late 1990s, The Garden of Sinners follows the story of Shiki Ryougi, a teenage girl raised as a demon hunter who acquired the "Mystic Eyes of Death Perception" after surviving a fatal accident. It also chronicles Mikiya Kokutou's unwavering efforts to get closer to her when they were still high school students and their adventures later on in dealing with supernatural cases as investigators for Touko Aozaki's detective agency, Garan no Dou. This is set in an alternate universe to Tsukihime and Fate/stay night in which it serves as the prototype for both series as well as introducing many of the concepts prevalent within the latter two.
The story starts following an incident: a young girl jumps from the top of a building. The image provokes a certain dread, as the girl appears to have been a corpse even before she jumped. The case is dismissed, yet more and more of these suicides occur, and all from the same building. Thus began the rumour, that a ghost inhabited the rooftop of the building.
August 1995: Mikiya first meets Shiki in a white kimono during a snowing day. Later on, at the high school freshmen ceremony, Mikiya sees Shiki in the crowd and chases after her, introducing himself to her. But Shiki hides a big secret: A wave of bizarre murders occur around many loose ends, and no suspects. there are still many questions: Who to believe? Who is the murderer? What is the secret of Shiki? and especially: Who is SHIKI?
July 1998 - After a group of delinquents is found dead in their hangout place with all their limbs twisted and torn off, Aozaki Touko receives a request to find the murderer and asks Shiki for help. The main suspect is Asagami Fujino; a girl who was the boys' plaything until recently, who Shiki believes to be "one of her kind".
June 1998: After spending two years in a coma caused by a traffic accident, Shiki Ryougi awakens with amnesia. She is visited by Touko Aozaki, a wizard and proprietor of a studio called Garan no Dou. Shiki has lost not only the memory of her accident, but also any real sense that she's even alive. Strangely, enigmatic beings begin to attack her...
Tomoe Enjou is attacked by bullies from his old school and saved by Shiki Ryougi. He asks her to hide him at her place and admits that he killed someone. Several days later, there are still no broadcasts about the murder as if it didn't happen... and when the victims are found, they're alive and unharmed.
January 1999: Apprentice mage Azaka Kokutou, Mikiya's younger sister, has been ordered by her mentor, Touko Aozaki, to investigate a certain incident in which fairies steal the memories of students at Azaka's school, Reien Academy. Azaka launches an investigation with the help of Shiki.
In February 1999, a string of murders has Shiki Ryougi and Mikiya Kokutou on edge. These crimes share a disturbing resemblance to a similar set of homicides from 1995, when Shiki and Mikiya first met, and awaken a dark, murderous desire that has laid dormant within Shiki's soul ever since then.
March 1999: Mikiya Kokutou meets Shiki Ryougi again at the same place where he met her for the first time four years ago...