Purpose: To analyze the dependence between corneal endothelial cell loss by Aqualase® cataract surgery and the nuclear opalescence grade of the lens. Patients and Methods: A total of 100 eyes of 92 patients were enrolled in this prospective, single-center study. Patients were randomly assigned to the Aqualase (50 eyes) or the phacoemulsification group (50 eyes). The nuclear density was classified with the Lens Opacities Classification System III. All procedures were performed by the same surgeon. Preoperatively and 1 week postoperatively, endothelial cell counts were obtained using a noncontact specular microscope (Konan, Japan). Results: (1) Aqualase group: the group of patients with a nuclear density of 1-2 (17 patients) showed no significant endothelial cell loss (4.1%, p = 0.163). The endothelial cell loss in grade 3 cataracts (28 eyes) was 13.9% (p = 0.004) and in grade 4 cataracts (5 eyes) 69.1% (p = 0.043), being statistically significant in both groups. (2) Phacoemulsification group: in nuclear density groups 1 and 2, endothelial cell loss was 6.3% (p = 0.41), in group 3 it was 17.6% (p = 0.001) and in group 4 it was 14.9% (p = 0.08). Only in nuclear opalescence grade 4 there was a significant difference between the Aqualase and the phacoemulsification procedure (p = 0.008). Conclusion: Endothelial cell loss by Aqualase technology depends strongly on the nuclear opalescence grade. In low- and medium-density cataracts, Aqualase does not seem to provoke significant endothelial cell loss. Due to very high endothelial loss in hard nuclei, Aqualase is unsuitable for these cataracts.