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Purpose: Medication non-adherence in dialysis patients is associated with increased mortality and higher healthcare costs. We assessed whether medication adherence is influenced by specific psychometric constructs measuring beliefs about the necessity for medication and concerns about them. We also tested whether medication knowledge, health literacy, and illness perceptions influenced this relationship. Patients and Methods: This study is based on data from a cross-sectional in-person questionnaire, administered to a random sample of all adult dialysis patients at a teaching hospital. The main outcome was self-assessed medication adherence (8-Item Morisky Medication Adherence Scale). The predictors were: concerns about medications and necessity for medication (Beliefs About Medication Questionnaire); health literacy; medication knowledge (Medication Knowledge Evaluation Tool); cognitive, emotional, and comprehensibility Illness perceptions (Brief Illness Perception Questionnaire). Path analysis was performed using structural equations in both covariance and variance-based models. Results: Necessity for medication increased (standardized path coefficient [β] 0.30 [95% CI 0.05, 0.54]) and concerns about medication decreased (standardized β − 0.33 [− 0.57, − 0.09]) medication adherence, explaining most of the variance in outcome (r2=0.95). Medication knowledge and cognitive illness perceptions had no effects on medication adherence, either directly or indirectly. Higher health literacy, greater illness comprehension, and a more positive emotional view of their illness had medium-to-large sized effects in increasing medication adherence. These were indirect rather and direct effects mediated by decreases in concerns about medications (standardized β respectively − 0.40 [− 0.63,-0.16], − 0.60 [− 0.85, − 0.34], − 0.33 [− 0.52, − 0.13]). Conclusion: Interventions that reduce patients' concerns about their medications are likely to improve adherence, rather than interventions that increase patients' perceived necessity for medication. Improving patients' general health literacy and facilitating a better understanding and more positive perception of the illness can probably achieve this. Our study is potentially limited by a lack of generalizability outside of the population and setting in which it was conducted. [ABSTRACT FROM AUTHOR]