If the conditions are right and configuration of aircraft entry systems coincides, then yes it is possible to open an aircraft door in flight. Ideally, this is not something that you should aspire to do. Nor, should you attempt this at home. There would be some stiff legal penalties for even attempting to open a door in flight aboard a commercial aircraft.

There have been several instances in flight where the aircraft doors have open in flight. Depending on the design of the door and aircraft, the opening of the door could disrupt the airflow and possibly cause for loss of control.
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If an aircraft is not pressurized, most of its doors usually can be unlatched without much effort.
As aircraft climb to the higher attitudes beyond 10,000 ft, systems are required to pressurize the aircraft. If the aircraft is at a fairly high altitude, the pressurization can be maintained that the cabin altitude pressure 6000 to 8000 ft. To attempt to open a door in flight at these altitudes would be rather difficult.
With the aircraft pressurized, the forces required to get the door to move would be astronomical taking into consideration the forces exerted inside the cabin outward. Some doors open outward. Other doors may go up into the ceiling of the aircraft. And some doors may open to the inside. In many cases the aircraft door acts as the “plug of the drain in the tub” preventing the escape of matter from the cabin to the atmosphere.
In addition to the air pressure, there are mechanical, electrical locks, and sensors in place for the aircraft doors. This essentially makes it possible for the crew to lock and know the status of the aircraft doors.
Another thing to consider is, that in the event of an emergency, the crew may not be available and able to open the door, so it is possible for the passenger to open the door in that event.
As most aircraft sit fairly high off the ground, there are emergency slide mechanisms that have to be dealt with when operating aircraft cabin exits.
In addition to the pressurization, we have the speed at which the aircraft flies and the corresponding drag and wind resistance. Since the aircraft is flying forward, that wind is resisting an going the opposite direction of the plane. If in the case you were to get the door open, you would most possibly be sucked out and blown into the airstream.
As the aircraft taxis to the gate, you may sometimes hear the cabin crew announcing โdoors to manualโ or โdisarm doors.โ This is the crew acknowledging and overriding the automating deployment function of the slides. These emergency slides can expand quickly with enough force to cause blunt force injury or death.

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