The department said Gates would be talking on, "how Microsoft will be working with the NHS to improve NHS IT".
According to Jenny Duff, public sector industry manager at Microsoft, the aim is "to get chief executives involved in the implementation of IT and not just delegate".
Gates will speak alongside a heavyweight NHS line-up including health secretary Alan Milburn, health service chief executive Nigel Crisp, and head of NHS research and development Professor Sir John Pattison.
The Gates speech is one of a series of public sector events, to be held in the same hotel, on 6 December.
Invitations have been sent to 150 specially chosen NHS chief executives, about a third of the total. "We're targeting the middle ground," said Duff.
The conference follows October's Enterprise Agreement between the NHS and Microsoft.
Computer Weekly understands that Microsoft offered the NHS the opportunity to be addressed by Gates during negotiations on the deal.
Some health IT industry insiders believe that Gates' personal appearance forms part of efforts - by both Microsoft and the DoH - to bed down the October deal on NHS-wide software subscription and extract maximum public relations value from it.
Others point out that the NHS contract is a done deal, and question whether it offers a sufficiently compelling reason on its own for Gates to come to London.
Gates' presence may be linked to Microsoft's ongoing dialogue with top echelons of the UK Government on how the software giant can help deliver NHS modernisation, and may even provide the platform for a major announcement.
"We expect Milburn to make some big announcements," confirmed Duff, adding that the event would address public-private partnerships in their broader sense.
A senior NHS IT figure confirmed to Computer Weekly that Microsoft was making strong representations to the Government that modernisation could only happen if key areas of NHS IT were contracted out.
A consortium of technology firms could be handed a geographic area and given central funding to implement the NHS IT strategy, he suggested.
Murray Bywater, director of analyst firm Silicon Bridge Research, said that big IT firms like Microsoft had a lot to offer. "You need heavyweight people to put in heavyweight systems, and the Government is impatient to see results," he added.
But big firms were no panacea, Bywater said, and the NHS had been badly burned with centrally imposed IT systems in the past.