The European Union has barred most of the planes of Pakistan International Airlines from flying to the 27-nation bloc because of safety concerns.
Pakistan grounded PIA's Fokker fleet after a crash last July
The ban affects 35 of the airline's fleet of 42 aircraft, with just seven Boeing 777s exempted.
The EU said last year it would ban flights unless the airline revamped its ageing fleet.
PIA said last week it strongly opposed the planned ban, which it did "not consider justifiable".
The airline's flights to London, Paris, Rome and Amsterdam will be among those affected.
The EU said it based its ruling on safety concerns surrounding the condition of PIA's fleet of 747s and Airbus 310s.
The EU has allowed the airline to continue to operate its flagship 777s.
Last week, a team led by the airline's chairman and the Pakistan envoy to Brussels met with EU representatives to try to resolve the issue.
A PIA statement released after that meeting said it "strongly disagreed with the EU's proposed action and on the given facts does not consider it to be justifiable".
The ban spells further trouble for an airline once regarded as the best in Asia, observers say.
The routes affected are some of the most lucrative for the airline and will be a blow for its revenues, they say.
"I would say we will have to cut at least 15% to 20% of our European operations," a PIA official told Reuters news agency.
PIA took a large cut in its domestic and Middle Eastern revenues after the Pakistani government forced it to ground its outdated Fokker fleet.
The action was taken following a huge public outcry after a number of accidents involving the aircraft, one of which resulted in a crash killing 45 people in July 2006.
Separately, the European Commission, the EU's executive arm, removed Phuket Air of Thailand and the African carrier DAS Air Cargo from its list of banned aircraft after they made safety improvements.