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Background: One of the most common psychological problems among people who use drugs (PWUD) is cognitive impairments (CIs). Several studies show that the prevalence of cognitive impairments in PWUD is higher than in the general population. Objectives: The aim of the current study was to investigate the prevalence of CI and its related factors among people who inject drugs (PWID) in Iran. Methods: A cross-sectional study was designed among PWID in 2023. About 410 PWID were recruited using snowball and convenience sampling in four provinces in Iran. Demographic and clinical data, as well as the status of cognitive impairments, were collected using bio-behavioral and Montreal Cognitive Assessment questionnaires, respectively. We examined the relationship between all independent variables and CIs status using bivariate logistic regression. Results: The prevalence of CI among participants was 28% (95% confidence interval (CI): 22% - 32%). Behaviors associated with an increased risk of CIs included the length of injecting drug use [adjusted odds ratios (aOR) = 2.7, P = 0.01], methamphetamine use (aOR = 2.8, P < 0.05), and alcohol use (aOR = 2.8, P < 0.05). Conclusions: Methamphetamine and alcohol use were identified as the main predictors of cognitive impairments among PWID. It also seems necessary to consider new interventions in harm reduction programs to address cognitive impairments. [ABSTRACT FROM AUTHOR]