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O'Kane became a stand-up comic in 1996 and got into the finals of the BBC New Comedy Awards of that year. She has played at the Edinburgh Festival every year since including 2001 where she not only performed her own solo show, Deirdre O'Kane is Crystallized, but also the two-hander Tis Pity She's Anonymous. She has also played The Melbourne, Adelaide and Kilkenny Cat Laughs Festivals and has toured the Middle East, Hong Kong, Shanghai, Prague, Brussels and London.
O'Kane began her career as an actress and has played every major theatre in Ireland as well as touring in Australia, Canada and the UK. Leading roles include Mary in Juno and the Paycock (National Theatre), Miss Funny in At the Black Pig's Dyke (Druid Theatre Co.) and Daphne in Present Laughter (Gate Theatre).
She portrayed the role of Noeleen in the 2003 motion picture Intermission, directed by John Crowley. She played the lead role in the 2014 biopic Noble as Christina Noble, a children's rights campaigner, charity worker and writer, who founded the Christina Noble Children's Foundation in 1989.
Television credits include hosting the ten-part TV series of stand-up comedy and sketches called The Lounge (RTÉ) which included guests such as Rich Hall, Adam Hills, Jeff Green and Dara Ó Briain. She also played the role of Fiona in Owen O'Neills sit-com The Fitz (BBC).
In 2001, O'Kane (described in The Sunday Times as "absolutely superb") played the leading role of Helen in Paths to Freedom, a six-part spoof-documentary for RTÉ/BBC Choice and starred in the RTÉ comedy series, Fergus's Wedding.
Starting in 2012, she plays the part of Debra Moone, in Sky's comedy Moone Boy.
In 2016, she made a guest appearance on the British TV show As Yet Untitled and told an anecdote about her car being double clamped by over efficient clampers to whom she was rude over the phone. Alan liked her stories enough to consider naming the episode after one of her quotes: "Would you ever fuck off?".
Deirdre is one of the narrators of the Irish version of Gogglebox, alongside Rory Cowan which started in 2016 on TV3. In 2018 Deirdre was a contestant on the second series of Dancing With The Stars.
- "'I lied about my age for 20 years' says Deirdre O'Kane as she reveals she turns 50 on day of DWTS final - Independent.ie". Independent.ie. Retrieved 2018-03-02.
- "I am from Drogheda even if Wikipedia says I'm from Dundalk", Deirdre O'Kane in interview with Miriam O'Callaghan, 27 August 2016, RTÉ 1.
- "Deirdre O'Kane admits that married life is a 'circus'". evoke.ie. 18 September 2015.
- Deirdre O' Kane - Her Brilliant Career!. RTÉ, 2008. Retrieved 5 July 2008.
- Deirdre O'Kane Archived 2013-05-05 at Archive.is. nyt.co.uk. Retrieved 5 July 2008.
- "'I do think we're funnier' - Host Deirdre O'Kane says Irish Gogglebox will be better than UK version - Independent.ie". Irish Independent. 21 September 2016. Retrieved 1 December 2016.