Two pilots, a special 'wellness' menu and more than seven weeks' worth of film and television entertainment were expected to accompany travellers on the 16,700-kilometres journey to the Big Apple.
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Singapore Airlines Flight SQ22 will use the long-range Airbus A350-900ULR, configured to carry 161 passengers - 67 in business class and 94 in premium economy.
For the flight crew - which also includes two first officers and a 13-strong cabin contingent - the workload will be broken up, the airline said, with every person getting a mandatory minimum four hours' rest.
But for passengers, the challenge will be what to do with all that down time up in the air.
For those not packing a weighty novel (or two), there will be 1,200 hours of audio-visual entertainment to choose from.
Dining options will include dishes the airline says have been selected to promote well-being in the skies, with organic dishes on the menu.
The cabin has higher-than-normal ceilings, larger windows and lighting designed to reduce jet lag -- all part of an effort to lessen the stresses that can accompany almost a day on a plane.
"Research has shown that hydration and food intake are important factors [to consider], such as avoiding foods that cause gas or bloating as well as excessive alcohol," Rhenu Bhuller, a healthcare expert at consultancy Frost & Sullivan, told AFP.
"The biggest concern is Deep Vein Thrombosis from a combination of sitting for too long and also from dehydration," said Gail Cross, an associate consultant at the National University Hospital in Singapore.
The twin-engine plane that will make the journey uses a modified system that burns 25% less fuel compared to other aircraft of a similar size, Airbus said.
The flight from the city-state to Newark Airport can take up to 18 hours and 45 minutes under normal weather conditions, but the pilots will have something in reserve in an aircraft capable of flying more than 20 hours non-stop.
Singapore Airlines originally flew the route for nine years using the gas-guzzling, four-engine A340-500 before abandoning it in 2013 because high oil prices made the service unprofitable.
But the carrier is hoping that the introduction of more fuel-efficient planes will set cash registers ringing even as crude prices soar above $80.
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Thursday's flight will top the current longest direct link between cities -- Qatar Airways Flight 921 from Auckland to Doha, which takes 17 hours 40 minutes.
"It's turning out to be a race between a few airlines eyeing the longest routes inter-continentally," said Shukor Yusof of aviation consultancy Endau Analytics.
"They are hoping to capitalise and exploit a very niche market," he told AFP.
Facing increasingly strong competition in recent years, Singapore Airlines has consolidated its low-fare subsidiaries and is strengthening its premium segment.
"Ultra-long haul services comprise an important component of that strategy," an airline spokesman told AFP.
The company is the first airline in the world to operate the A350-900ULR plane. It received the first aircraft in September. Six more are due for delivery by the end of the year.
"We are optimistic about the demand for non-stop services to the US," the spokesperson said.
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