Among patients with end stage renal disease (ESRD), the Non-adherence to phosphate binder medications represents a big contributor for hyperphosphatemia management failure. Hence, it makes the patient prone for high risk of cardiovascular morbidity and all-cause mortality as a consequence of hyperphosphatemia. Thus, we tend in this study to investigate whether there is an association between adherence, knowledge, serum phosphate, and any of patient demographic characteristics affecting phosphate binder adherence. This study is a cross sectional, descriptive, single arm, multicenter study for the purpose of evaluating the patient adherence and knowledge toward phosphate binder medications in hemodialysis patients with hyperphosphatemia. This study was conducted at the Nephrology Centers in Al-Sader Medical Teaching City and Al-Hakeem General Hospital in a period from January to May 2021. The study population consist of 75 hemodialysis ESRD patients on chronic dialysis with a mean age of 41.13±11.40 years. The non-adherence status for phosphate binders was prominent by 81.33%. A 32 % of patients was receiving three hemodialysis treatments per week. The mean serum phosphate levels were 6.96±0.73 mg/dl. A significant inverse correlation was seen in adherence when compared with serum phosphate level (P<0.05). While the adherence correlates significantly with patient knowledge toward phosphate binders (P = 0.0071). Circulating phosphate level was affected by the extent of adherence to the usage of phosphate binders. Furthermore, the patients' knowledge towards phosphate binders might be important for patients’ motivation for being adherent.