The Skymaster's unique sound is made by its rear pusher propeller slicing through turbulent air from the front propeller and over the airframe while its front tractor propeller addresses undisturbed air. Federal Aviation Administration Airworthiness Directive 77-08-05 prohibits single-engine take-offs and requires the installation of a placard marked 'DO NOT INITIATE SINGLE ENGINE TAKEOFF'. Accidents have occurred when the runway is shorter than the single-engine take-off roll and pilots, unaware of a rear engine shutdown, have attempted take-off on the nose engine alone. The rear engine tends to overheat and can quit while taxiing on very hot days. Ground handling requires certain attention and procedures. Flying a Skymaster requires a pilot to hold a multiengine rating, although many countries issue a special 'centerline thrust rating' for the Skymaster and other similarly configured aircraft.

With no one-engine-out minimum controllable speed (Vmc), in-flight control at any flying speed with an engine inoperative is not as critical as it is with engines on the wing with the associated leverage however, performance in speed and, particularly, rate of climb are affected. Without the issue of differential thrust inherent to conventional (engine-on-wing) twins, engine failure on takeoff will not produce yaw from the runway heading. The Skymaster handles differently from a conventional twin-engine aircraft, primarily in that if an engine fails, the plane will not yaw toward that engine.

Cessna 337 skymaster manual