Abstract Background: Diabetes frequently results in the need for multiple medication therapies, known as ‘Polypharmacy’. This situation can incur significant costs and increase the likelihood of medication errors. This study evaluated the prescriptions of patients with diabetes regarding polypharmacy to assess its effect on the control of hemoglobin A1c (HbA1c) levels and prescription costs. Methods: A cross-sectional national study was conducted based on data from linking the Iranians Health Insurance Service prescriptions in 2015 and 2016 with the STEPS 2016 survey in Iran. The association of the individual and sociodemographic factors, as well as polypharmacy, as independent variables, with control of HbA1c levels and the cost of the prescriptions were assessed among diabetic patients using logistic and linear regression, respectively. Results: Among 205 patients using anti-diabetic medications, 47.8% experienced polypharmacy. The HbA1c of 74 patients (36.1%) was equal to or less than 7, indicating controlled diabetes. HbA1c control showed no significant association with gender. However, prescription costs were notably lower in females (β = 0.559 [0.324‒0.964], P = 0.036). No significant correlation was found between the area of residence and prescription costs, but HbA1c was significantly more controlled in urban areas (OR = 2.667 [1.132‒6.282], P = 0.025). Prescription costs were significantly lower in patients without polypharmacy (β = 0.211, [0.106‒0.423], P < 0.001), though there was no significant association between polypharmacy and HbA1c levels. Conclusion: Our results demonstrated that diabetics with polypharmacy paid significantly more for their prescriptions without experiencing a positive effect on the control of HbA1c levels. Keywords: Cost, Diabetes, Hemoglobin A1c, Polypharmacy Cite this article as: Daneshmand M, Jamshidi H, Farjoo MH, Malekpour M, Ghasemi E, Mortazavi SS, et al. Assessment of hemoglobin A1c management and prescription cost due to polypharmacy among patients with diabetes in Iran based on the STEPS Iran 2016 survey and a prescription database: a multi-level, cross-sectional national study. Arch Iran Med. 2024;27(1):1-7. doi: