We report on a study to determine the effect of waveguide side-wall roughness on Quantum Cascade (QC) laser performance, such as threshold current density, slope efficiency, far-field beam pattern and group refractive index, using two two-wavelength heterogeneous cascade QC laser structures, one with emission wavelengths of 7.0 μm/11.2 μm, and the other with 8.7 μm /12.0 μm. For the range of roughness standard deviation values from about 0.4 μm to 1.0 μm for which all four QC lasers were operating, the threshold current density increases by 12%-15% and the slope efficiency decreases by 30%-70% with stronger performance degradation for the shorter wavelength lasers, which is in agreement with a model based on Rayleigh scattering. Moreover, no significant change in the far-field beam patterns for different σ rough values was observed, and the group effective index values of the four wavelengths have several values for each rough waveguide indicative of multiple transverse modes in the waveguides.