The TV presenter and entertainer will play cancer patient Tim Connor in the medical drama, appearing in three episodes from September.
O’Grady said: “I’m a big fan of Holby City so to be featuring in three episodes is absolutely brilliant.”
Oliver Kent, Holby‘s Executive Producer added: “Having Paul appear in Holby City is such a great coup for the show. Paul has a vibrant personality and a very unique way of engaging with the audience – not to mention he’s incredibly funny. This is exactly what we need for a storyline that will be filled with a rollercoaster of emotions.”
Although best known for his long career as an entertainment host and the star behind popular drag act Lily Savage, O’Grady has had previous acting roles with Eyes Down and The Bill among his credits.
Holby City continues on Tuesday at 8.00pm on BBC One.