Anne Ramsey's speech impediment was caused by operations she underwent in order to treat throat cancer. During filming she was undergoing additional oral surgery and endured intense pain. However, according to director Danny DeVito, she never requested to be excused from work. "Momma" went on to become Ramsey's most critically-lauded performance, culminating with Academy Award nomination for Best Supporting Actress in 1988. Sadly, she died only six months after the ceremony because of that very same throat cancer.
Orion needed to approach Warner Bros. about getting permission to use the references to Strangers on a Train (1951), but Warner wasn't keen to cooperate. Warner realized that Orion still owned the rights to Arthur (1981), so they traded the Alfred Hitchcock classic to make an "Arthur" sequel. Arthur 2: On the Rocks (1988) turned out to be a complete disaster at the box office, whereas "Throw Momma from the Train" was the 13th most successful movie of 1987.
Danny DeVito once noted in an interview with Playboy Magazine that the scene where Owen shows his coin collection to Larry was inspired by his childhood habit of sharing things with friends that involved whatever he was into at the time. As director, he insisted on including such a sequence in the movie. Writer Stu Silver wrote the scene.
Anne Ramsey slaps Danny DeVito's face for real. While she was hesitant to do so, DeVito insisted on a real slap.