The part outline and part detailed applications set out plans to build a 375,000 sq ft mixed-use development on disused land around the hospital and nearby football stadium.
This will include new hospital facilities for Watford and south-west Hertfordshire, 750 homes and 37,500 sq ft of offices
VolkerFitzpatrick will start work on an 18-month project at the end of this year to build a £7m link road from the development site to the M1.
Phil Woods of Kier Project Investment said: “The masterplan vision reflects concepts and ideas received from stakeholders, the public and partners since the project was conceived over 10 years ago.
“The project team has worked hard to meet the ambitions for the scheme by creating a first-class vision for the area.”
If the plans are given the green light, work could start on the business areas, the first zone of the 29 hectare site earmarked for development, as early as next year.