Silicon photonics is a promising technology for the fabrication of dense photonic chips, thanks to the very mature silicon industry. The direct epitaxial growth of III–V lasers on silicon is one of the main challenges for the realization of compact and robust mid-infrared sensors based on photonic integrated circuits. The crystal defects arising from this heteroepitaxial growth affect the laser performance and, therefore, need to be mitigated but also studied to better understand their impact on the laser operation. Here, we studied the effect of threading dislocations on laser performance by comparing the series of GaSb-based diode lasers grown on native GaSb and Si substrates with different numbers of quantum wells ( nQW) in their active zones. As expected, the laser threshold currents are higher in the case of diode lasers on Si, and they rapidly vary with nQW. Still, the lowest threshold current densities are achieved with nQW = 1 for both substrates. With the help of a theoretical gain model, we attribute these results to the fact that dislocations create non-radiative recombination but do not introduce additional optical losses. This work allows a better understanding of the origin of performance degradation and the decision to be made regarding the heterostructure design.