By evaluating preoperative endothelial cell density (ECD), ECD loss after phacoemulsification can be predicted. In this retrospective cross-sectional study, we compared outcomes of phacoemulsification with different levels of preoperative ECD. Three-hundred-and-fifty-three patients aged between 18 and 90 years received phacoemulsification at Chang Gung Memorial Hospital. Age (p = 0.003), preoperative logMAR (p = 0.048), cataract grade (p = 0.005), preoperative ECD (p < 0.001), operation time (p = 0.043), phacoemulsification time (p = 0.001), and phacoemulsification energy (p < 0.001) were significantly associated with postoperative ECD change (%). Patients were divided into three groups according to preoperative ECD levels. Level of ECD, coefficient of variation (CV), cell hexagonality (HEX), central corneal thickness (CCT), visual acuity, underlying diseases, and complications were analyzed. With regard to groups, 29, 71, and 252 patients were respectively allocated into the markedly low (group A; ECD below 1000 cells/mm²), mildly low (group B; ECD between 1000 to 2000 cells/mm²), and normal (group C; ECD above 2000 cells/mm²) ECD level groups. The highest CV (40.8 ± 13.9%; p < 0.001) and lowest HEX (58.4 ± 14.6%; p < 0.001) were found in group A. Significant ECD loss was found in group B (28.9 ± 9.2%) as compared to group A (19.9 ± 5.4%) and C (15.0 ± 12.0%) (p < 0.001). No significant differences were found with regard to changes in CV (p = 0.941), HEX (p = 0.937), CCT (p = 0.346), and logMAR (p = 0.557) among the three groups. In conclusion, preoperative ECD level could be a novel predictive value for postoperative cell loss, which was the most prominent in mildly low ECD level group. Less phacoemulsification energy, earlier surgical intervention, or novel topical medications could be suggested for patients with an ECD range from 1000 to 2000 cells/mm².

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