Michael Crichton originally wrote the screenplay in 1974 under the title 'EW' (for Emergency Ward), based on his own experiences as a medical student in a busy hospital emergency room, but producers weren't interested at the time.

After Jurassic Park's success, Crichton and Steven Spielberg revisited the ER script, and Spielberg decided to turn it into a two-hour television pilot rather than a feature film.

The pilot script used in 1994 was virtually unchanged from Crichton's 1974 draft; the only substantive changes were turning a male character into a female one (Susan Lewis) and changing Peter Benton's race to African-American.

Due to a lack of time and money to build a set, the pilot episode was filmed in the former Linda Vista Hospital in Los Angeles, a facility that had already closed in 1990.

After the pilot, a permanent set modeled after Los Angeles County General Hospital's emergency room was built at Warner Bros. Studios in Burbank, though the show also used extensive location shoots in Chicago, notably the city's 'L' train platforms.

The 1997 episode 'Ambush' was broadcast live twice, once for the east coast and again three hours later for the west coast.

The 2002 episode 'Hindsight' was told in reverse chronological order, following Dr. Kovač through a Christmas Eve shift and the party that preceded it.

Nurse Carol Hathaway, played by Julianna Margulies, attempts suicide in the original pilot script but was ultimately made into a regular series cast member.

Sherry Stringfield was the first original cast member to leave the series in season three; contrary to rumors that she wanted more money, she actually left because she disliked the fame the show brought her, later returning from 2001 to 2005.

James Newton Howard composed the score for the two-hour pilot and the show's original theme, while Martin Davich scored all subsequent episodes and wrote a new theme used from 2006 to 2009, with Howard's original theme returning for the series finale.

The show's highest-rated episode, 'Hell and High Water,' drew 48 million viewers and a 45% market share, the highest for a regularly scheduled drama since a May 1985 episode of Dallas.

The series finale commanded $425,000 per 30-second ad spot, more than three times the season's standard rate of $135,000, while the show cost a record $13 million per episode between seasons 4 and 6.

A 2024 lawsuit from Michael Crichton's estate alleged that the medical drama The Pitt, starring original ER actor Noah Wyle and produced by original showrunner John Wells, was actually an unauthorized ER remake; Warner Bros. denied this, calling it an original show.