Her tome, set in the Amazon, about a life-altering drug, is contending with novels exploring subject from adultery to ancient Greek love, to wartime atrocities in Romania.
The 17th annual Orange Prize, which celebrates women’s fiction, has put six novelists in the running.
Half of them are American writers: Patchett, Madeline Miller and Cynthia Ozick, who, at 84, is the oldest writer to have been shortlisted. There was one Briton, Georgina Harding, an Irish writer, Anne Enright, and the Canadian Esi Edugyan.
Joanna Trollope, chair of the judging panel, said: “This is a shortlist of remarkable quality and variety. It includes six distinctive voices and subjects, four nationalities and an age range of close on half a century. It is a privilege to present it.
“My only regret is that the rules of the prize don’t permit a longer shortlist. However, I am confident that the 14 novels we had to leave out will make their own well-deserved way.”
The Forgotten Waltz by Enright, another shortlist heavyweight, follows a woman’s calamitous affair.
Harding’s Painter of Silence is the story of a gifted deaf man, set in post-war Romania.
Edugyan’s Half Blood Blues also made the cut in last year’s Man Booker shortlist, and tells the story of black jazz musicians in Nazi-occupied Paris.
Miller debuts with a book about the love between Achilles and Patroclus, and Ozick’s Foreign Bodies follows the story of a woman grappling with life as a middle-aged woman alone in 1950s New York.
The winner will be announced on May 30.