Barrowman will be guest starring in one episode of the drama, playing the role of visiting consultant Drew Nicholson-Heath who has some history with Ange Godard (Dawn Steele).
And it's Ange who bumps into Drew in the soap's new Spring trailer, and it's not long before she's questioning what he's doing here.
"Slumming it, I guess," Drew replies.
The soap has teased that renowned global recruiter Drew is always on the look out for talented, new surgeons to poach, and his arrival in Holby City soon has certain members of the team trying to impress him.
"Being part of another iconic BBC drama is just fabulous," Barrowman said in a statement.
"I was welcomed with open arms by the cast and crew and felt like part of the Holby City family right away. My character Drew brings a new flavour to the show and I look forward to his return soon. Surgery will never be the same again."
Elsewhere, the soap is lining up a rollercoaster few months ahead for the staff and patients at Holby City Hospital, with the trailer also teasing the return of Guy Self (John Michie) and his growing tensions with Ric (Hugh Quarshie), while Essie (Kaye Wragg) and Fletch (Alex Walkinshaw) are thrown into turmoil as they receive life-threatening cancer diagnoses.
"Showing the real struggle of two nurses sharing an illness together yet being alone in their own torture of what their futures hold is Holby at its best," Kaye said of the storyline, which sees Essie's cancer return.
"Being immersed in the world of this disease is something I've had many experiences with as myself, so there's no shortage of empathy and understanding for my character and for Fletch's.
"It's a tough watch, but it will resonate for many sufferers and their loved ones going through traumatic illnesses. Throughout their journeys, Essie and Fletch discover their worst fears, their lost opportunities and what futures they need to make plans for."
Holby City continues on Tuesday (March 10) at 8pm on BBC One.
Digital Spy now has a newsletter – sign up to get it sent straight to your inbox.
You Might Also Like