The World Trade Organisation has ruled some European governments paid planemaker Airbus prohibited export subsidies.
The WTO – responding to complaints against Airbus from its US rival Boeing – said the subsidies must stop.
The European Commission voiced disappointment and is deciding whether it will appeal.
The WTO dispute panel decided that most loans for the A380, the world’s largest airliner, were illegal.
Airbus disputes a Boeing statement that it will now have to pay back around 3.25 billion euros.
US Transportation Secretary Ray LaHood said the judgement sends a strong signal to European countries on future subsidies.
Boeing said the decision proved Airbus had only been able to take market share and become the number one airline manufacturers because of subsidies.
But Brussels has brought a counter suit and in mid July the WTO is likely to rule that Boeing also benefited from illegal US government subsidies, notably $5 billion in non-repayable aid for its 787 Dreamliner.
At that point the two parties may decide to negotiate a settlement to their differences over the funding of large civil aircraft, although the WTO rulings will still be available to other countries that want to challenge them.