In 1999, Darrow played a large role in Analyze This with Robert De Niro and Billy Crystal. The following year, he appeared in Mickey Blue Eyes with Hugh Grant, and got another big role as mobster Larry Barese in the HBO hit series The Sopranos, which he was on for the entire series run (1999–2007). More recently, Darrow starred in the independent film Lynch Mob.

In June 2009, Darrow was charged with extortion in a 2004 incident. Along with Gambino crime family soldier Joseph “Joey Boy” Orlando and associate Giovanni “Johnny” Monteleone, Darrow was accused of ordering the maiming of a man in Monticello, New York who owed money to a loan shark. Darrow and Orlando both pleaded guilty in federal court to these charges on February 2011, in exchange for a sentence of up to 33 months. However, Monteleone cooperated with the FBI. At sentencing, Darrow’s attorney successfully argued that Darrow’s 50+ year history of community service, medical condition, and lack of prior criminal history warranted a sentence of house arrest, followed by a period of probation. Orlando was sentenced to 51 months in prison and Darrow received six months of house arrest.