
Industry leaders demand urgent reform and leadership changes at Nats following widespread flight cancellations and delays across the UK.
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Nats experienced a separate software defect at Swanwick earlier in September that led to the cancellation of 2,000 flights.
Airlines have criticised the UK's air traffic control over a second glitch this month that has caused flight delays and cancellations.
EasyJet said Monday's incident "once again calls into question the resilience" of the system, while Wizz Air said there was a "national confidence crisis" in Nats, which runs the UK's air traffic.
The technical problem at Prestwick in Ayrshire caused disruption at airports across Scotland, Northern Ireland and northern England, delaying dozens of flights.
Nats said a "connectivity issue" was to blame for the disruption, and that it had "nothing to do" with a separate software defect at Swanwick that led to the cancellation of 2,000 flights earlier in September.
The underlying issue causing Monday's disruption has since been resolved, with Nats saying it was running at "full capacity" although officials warned of knock-on effects.
A spokesperson said they were now "focused on working with our customers to recover their residual delays and help get their operations back to normal".
According to aviation analytics company Cirium, as of 13:45 BST, at least 200 flights had been cancelled or did not fly on Monday. This includes 100 flights scheduled to arrive in the UK and 99 that were due to depart from the UK.
Easyjet was the worst affected airline, with 47 of its 670 scheduled departures cancelled, while British Airways has seen 11 cancellations from its 513 scheduled departures.
Industry representative body Airlines UK said both passengers and airlines "deserve better" after "yet another Nats failure".
Managing director of Wizz Air UK, Yvonne Moynihan, called for "urgent reform" of Nats, adding that she did not have confidence in its current leadership.
When asked by BBC Radio 4's World at One programme whether Nats chief Martin Rolfe should resign, Moynihan said: "We need to look at the leadership at the top. But more than that, what are the board of directors doing?"
Jet2 boss Steve Heapy called for "urgent and accountable" action to bolster the UK's air traffic control infrastructure.
Ryanair reiterated its calls for Rolfe to resign, saying he had failed to deliver" either a reliable system or an effective back-up". The latest outage affected 140 of the airline's flights and 25,000 passengers.
British Airways said "yet another technical fault with Nats" was "disappointing".
A Nats spokesperson apologised for the disruption, saying: "In the real world, we accept technology can and sometimes does fail. Our job is minimising disruption where possible.
"What isn't acceptable is any incident where safety is compromised - this is always our first priority."
They added that it was working to return air traffic to normal as quickly as possible and urged passengers to check their flight status with their airline.
Transport Secretary Heidi Alexander acknowledged the problems with flights were "deeply frustrating" for passengers.
Steve Davies, 74, told the BBC he was "cheesed off with air traffic control" as technical issues with its systems seemed to be "happening a lot".
He and his wife Sadie became stuck at Birmingham airport after being told to disembark their easyJet flight to Edinburgh on Monday morning.
Nicole McCloskey, from Kilmarnock, had been due to go to Disneyland Paris with her family before their flight was cancelled.
She told the BBC her family got a message to say the flight was delayed while they were travelling to Glasgow airport, but only found out it had been grounded altogether once they arrived.
Nicole said they have been rebooked on another flight today and were hopeful "it's sorted in time".

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