The "Stay You" campaign will promote Holiday Inn as a friendly and contemporary hotel chain, where guests can go to relax and be themselves.
The work will run across TV, press and online, and will air predominantly in the UK, US and Germany.
The overall global strategy has been developed by McCann Erickson, with McCann Erickson Manchester creating the work that will run in Europe.
The first UK TV spot will launch on 3 May on ITV1 during travel programme 'Joanna Lumley's Nile'.
The new campaign marks the first time that Holiday Inn has advertised on TV since 2002, and will see it challenge budget chains Premier Inn and Travelodge for share of voice.
Premier Inn has rolled out a number of TV ads in recent months starring comedian Lenny Henry.
Travelodge is breaking a new £10m campaign on Saturday (1 May) which will use TV for the first time in 20 years.
Andy Cosslett, the chief executive of InterContinental Hotels Group, said: "The level of support behind this campaign reinforces our confidence in the Holiday Inn relaunch which positions us well for the upturn in the economy when it comes."