An instruction set where all (or most) instructions have the same format and all registers and addressing modes can be used interchangeably - the choices of op code, register, and addressing mode are mutually indepentent (loosely speaking, the choices are "orthogonal"). This contrasts with some early Intel microprocessors where only certain registers could be used by certain instructions.

Examples include the PDP-11, 680x0, ARM, VAX.