The 8K72 was the first R-7 variant explicitly designed as a carrier rocket and it incorporated a few features that became standard on all later R-7 carrier rockets including thicker tank walls to support the weight of upper stages and the AVD malfunction detection system, which would terminate engine thrust if the booster's operating parameters (engine performance, electrical power, or flight trajectory) deviated from normal.

The resonant vibration problem suffered by the 8K72 booster was the cause of a major argument between the Korolev and Glushko design bureaus.

It was believed that the vibrations developed as a consequence of adding the Blok E upper stage to the R-7, shifting its center of mass.

[5] The fifth flight of a Luna 8K72 (18 June 1959), which was to launch the Luna E-1A No.1 probe, ended 153 seconds after launch due to a guidance malfunction of the Blok A core stage, leading to engine shutdown.

The ninth flight of a Luna 8K72 (April 1960), which was to launch the Luna E-3 No.2 probe, failed when the Blok G strap-on booster developed only 75% thrust at liftoff, breaking away from the launch vehicle, which then disintegrated, the strap-ons flying in random directions and exploding as they impacted the ground.