In 1912, he returned to the U.S. and in 1924 he married divorcee Cissy Hurlburt, 18 years older than he was. He first came to write detective stories in 1933 with the support of his wife. Blackmailers Don't Shoot, which took five months to write, was published by Black Mask, the leading crime pulp of its time which also published Dashiell Hammett's stories. Writing proved lucrative, and was something Chandler enjoyed, so he continued. His character Philip Marlowe, a 38-year-old P.I., a man of honor and a modern day knight with a college education, first appeared in the story Killer in the Rain, which later formed part of Chandler's first novel The Big Sleep (1939), and he turned to screenwriting in 1943. He met with some success writing for Hollywood - "And Now Tomorrow" (1944), "Double Indemnity" with Billy Wilder (1944), "The Unseen" (1945), and an original script, "The Blue Dahlia" (1946), and "Strangers On A Train" for Hitchcock (1951).

As representative and master of hard-boiled school of crime fiction, Chandler criticized classical puzzle writers for their lack of realism in his much quoted essay The Simple Art of Murder.

Chandler was a slow writer. Between 1933 and 1939 he produced a total of nineteen pulp stories, eleven in Black Mask, seven in Dime Detective, one in Detective Fiction Weekly. Unlike most of his pulp-writing colleagues, Chandler tried to expand the limits of the pulp formula to more ambitious and humane direction.

He and Cissy moved to La Jolla (north of San Diego) in 1946, where he continued writing while taking care of his beloved wife, who suffered from fibrosis of the lungs. In 1946 Chandler received Edgar Award from the Mystery Writers of America for screenplay, and in 1954 for novel. In 1954 Cissy, Chandler's wife of 30 years, passed away, after a lengthy illness. Chandler plunged more deeply than ever into drink, still managing to produce some of the English language's greatest crime fiction. Two months after her death, he attempted suicide, which was reported widely; the bullet caused major damage to the bathroom. During the last year of his life Chandler was president of the Mystery Writers of America. Playback, Chandler's last finished novel, appeared in 1958. He went into a slow decline, though he is said to have had a romantic interest in his secretary, Jean Fracasse, and later was preparing to marry his agent, Helga Green, when he died of pneumonia brought on by a particularly heavy drinking binge on March 23, 1959, at the age of 70.

His unfinished novel Poodle spring was completed by Robert B. Parker, who has also written a sequel to The Big Sleep, entitled Perchance to dream (1990).

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