It is shown that semiconductor lasers utilizing intersubband transitions in quantum boxes (IQB lasers) can have lower threshold current densities and operating voltages than quantum cascade (QC) lasers provided that a reduction factor of about 10 can be achieved in the LO phonon-assisted electron relaxation rate. The increased gain for the radiative stage in an IQB laser eliminates the need for a multi-radiative-stage structure (typically 25 in QC lasers). This allows the electron injector and Bragg mirror regions on either side of active region to be separately optimized. Due to their inherently lower input power requirements, IQB lasers operating in the mid-IR should be capable of cw operation at room temperature with high wall plug efficiency and higher average output powers than QC lasers.