The Irish low-cost carrier will offer 130 weekly flights from the airport, which is part of Manchester Airports Group (MAG), from April 2022.
Destinations from East Midlands will include key summer gateways such as Alicante, Barcelona, Chania, Lanzarote, Malaga, Majorca, Rhodes, Rome and Tenerife.
Jason McGuinness, Ryanair’s director of commercial, said: “We are delighted to have extended our long-term partnership with East Midlands, Manchester and Stansted airports who will now all benefit from Ryanair’s delivery of 210 Boeing ‘gamechanger’ aircraft.”