Owner Caroline Hirsch announced Tuesday in a social media post that she has decided not to renew the lease.
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The final shows will be on New Year's Eve.
However, Hirsch said she will continue to expand the Carolines brand and bring comedy to people in more places while continuing to grow the New York Comedy Festival through the city and the country.
"No matter the shape or form of Carolines' future platform, we will always shine a spotlight on emerging talent," Hirsch said.
Carolines launched in Chelsea 40 years ago before moving to the South Street Seaport and then finally to Times Square in 1992.
Hirsch said some people thought they were crazy to invest in Times Square at that time due to high crime, but later said they were ahead of the curve as global brands and national retailers came to the neighborhood.
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"We are very proud to have played an integral role in its resurgence and brought much needed laughter to the neighborhood and the city," Hirsch said. "We've had an incredible run these past 40 years, elevating comedy from the very beginning and we are so proud of the comedians that have graced our stages throughout the years with their considerable talents."
Hirsch thanked all the comedians, staff and comedy fans who have visited the club over the last four decades.
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