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Introduction: End‐stage renal disease is a serious public health issue. The objective of this retrospective cohort study was to assess the association between hemodialysis and cognitive impairment, while controlling for age, sex, residence, and comorbidities. Methods: This study assesses the risk of cognitive impairment among a nationwide cohort of new hemodialysis patients derived from the NHIRD. Results: A total of 4330 patients were assigned to the dialysis group and 17 320 patients were assigned to the control group. A total of 2103 of the patients developed cognitive impairment within 2 years after the date of dialysis initiation. Patients who developed cognitive impairment were older (69.85 ± 11.56) than their counterparts who did not develop cognitive impairment (58.58 ± 14.77; P <.001). The log‐rank test of Kaplan‐Meier analysis revealed a higher risk of cognitive impairment in the hemodialysis group than in the non‐hemodialysis group (P <.001). The interval between dialysis initiation and the onset of cognitive impairment was 98.66 ± 46.39 months among non‐dialysis subjects and 53.45 ± 41.90 months among dialysis subjects, and the between‐group difference was significant (P <.001). The Cox Proportional Hazard Model revealed that after controlling for gender, age, residence, and comorbidities, hemodialysis was shown to have a significant impact on cognitive impairment (Hazard Ratio [HR]: 1.44; 95% confidence interval [CI]: 1.29‐1.60). Furthermore, the risk of developing cognitive impairment increased with age (HR: 1.07; 95% CI: 1.06‐1.08). Discussion Hemodialysis was associated with cognitive impairment. There was a significant association between age and cognitive impairment, regardless of the comorbidities prior to hemodialysis. There was no evidence of an association between comorbidities and cognitive impairment after beginning hemodialysis. [ABSTRACT FROM AUTHOR]