In Peril at End House, retired detective Hercule Poirot becomes involved in the seeming murder attempts against Nick Buckley, the attractive young owner of a family mansion called End House. Nick's cousin Maggie Buckley is killed, presumably mistaken for Nick, and Poirot gets Nick to reveal that she's secretly engaged to airman Michael Seton and heir to a large fortune. After Nick becomes poisoned by chocolates laced with cocaine, Poirot eventually realizes that he's been mistaken all along. Nick was never the intended victim. She murdered Maggie to take her place as Seton's supposed fiancée and heir.

As the novel begins, Poirot is on vacation in St. Loo, when a bullet hits the wall by his head. He discovers that beautiful, young Nick Buckley has had three recent close calls with death, and he believes that someone is trying to murder her. Nick agrees to ask her cousin Maggie to her house to guard against danger. However, at a fireworks show the night that Maggie arrives, Maggie borrows Nick's shawl and is shot to death, presumably having been mistaken for Nick. Poirot rushes Nick off to a rest home, where visitors will not be allowed, for protection.

Poirot's list of suspects includes Nick's cousin Charles Vyse, a lawyer, who would inherit End House, Nick's family home, and Nick's friend Frederica Rice, a drug user who would inherit the rest of Nick's possessions. However, Nick has nothing of value to leave, and the house is mortgaged. Poirot has an inspiration, though. He realizes from how Nick has acted that she is secretly engaged to missing airman Michael Seton. Seton's rich uncle recently died, and Nick stands to inherit a fortune.

While Nick is in the rest home, she eats some chocolate poisoned with cocaine and Poirot reproaches himself for letting harm come to her. He has asked her to eat no food from outside the home, but the chocolates had Poirot's card in them. Poirot investigates and finds only confusion. Two boxes of chocolates were delivered, one by mail and one by hand. The one delivered by hand came from Lazarus, an art dealer friend of Nick's and a boyfriend of Frederica. Lazarus says Frederica told him to buy the chocolates, and Frederica says that Nick, or someone who said they were Nick, phoned and asked for them. Poirot is stumped.

Finally, Poirot has an epiphany. He realizes that Nick has been lying the whole time. She faked the accidents that Poirot thought were murder attempts, and she was never secretly engaged to Seton. Nick's cousin Maggie was Seton's fiancée, and Nick killed her so that she could take Maggie's place and inherit the money. Poirot stages a reading of Nick's will and a séance at the end of the novel, and he traps Nick into revealing the secret hiding place where she's put the murder weapon. Nick is arrested, but she asks Frederica for her watch, which contains a stash of cocaine. Nick plans to poison herself in actuality, this time.