In this study, the operational durability of laser diodes (LDs) with CdSe quantum dot (QD) active region is examined through a detailed comparison with its BeZnCdSe quantum well (QW) counterpart. To focus on the impact on the difference caused by the nature of the active region, other layers such as the waveguide layer, cladding layer, and contact layer, which influence the mode profile of the optical confinement and electrical properties, are maintained under the same condition. Although the threshold current of the CdSe QD LD is higher than that of the BeZnCdSe QW LD by a factor of 1.6–1.7 under a fresh condition, the degradation of the former proceeds much more slowly than that of the latter. This is confirmed by a reliability test conducted under the current injection condition both below and above the lasing threshold. The result indicates that the stronger carrier localization in the CdSe QDs compared to that in the BeZnCdSe QWs prevents the interaction with remote defects in the active layer. Consequently, the CdSe QD LD is less sensitive to degradation due to recombination-enhanced defect reactions.