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Background: Several studies have reported that iron-deficiency anemia (IDA) and its treatment might lead to a distorted reading of glycated hemoglobin (HbA1c) value. Hence, this review aims to systematically investigate the effect of iron replacement therapy (IRT) on HbA1c levels, as the literature is deficient in assessing this clinical phenomenon. Methods: An electronic search of the Cochrane, MEDLINE, and Embase databases was conducted by four independent authors. Results: Among the 8332 articles identified using the search strategy, 10 records (with a total of 2113 participants) met the inclusion criteria and were analyzed. In nine of the studies, IRT was found to decrease HbA1c levels; in the remaining study, IRT was found to increase HbA1c levels. The effect size of the pooled standardized mean difference in HbA1c levels between the treatment and control groups with IDA was 1.8 (95% CI = −0.5, 2.31). Heterogeneity was assessed using the I2 and χ2 tests, and the resultant values were 98.46% and p = 0.09, respectively. Additionally, the mean difference between the HbA1c levels (pre-IRT and post-IRT) showed a drop in the HbA1c levels which ranged from 1.20 to 0.43 mg/dL. Conclusions: The results suggest that IRT decreases HbA1c levels, and it is helpful in treating IDA patients with poor glycemic control. Accordingly, the results provide an added perspective on antidiabetic medication dosing and physicians' interpretation of initially elevated HbA1c values. [ABSTRACT FROM AUTHOR]