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Background More than one-third of reproductive aged women in Ethiopia use hormonal contraceptives to prevent conception. The present study aimed to compare the hematological parameters of reproductive-age women taking hormonal contraceptives at the University of Gondar Comprehensive Specialized Referral Hospital, Northwest Ethiopia in 2021. Methods A comparative cross-sectional study was conducted from April to June 2021. A total of 240 study participants were recruited by using a consecutive sampling technique. Data on socio-demographic variables and clinical data were collected through face-to-face interviews using a structured questionnaire and medical record reviews, respectively. Three milliliter venous blood was collected for complete blood count analysis using Unicel DxH 800 coulter hematology analyzer. Data was entered into Epi-data 4.4.3.1 version then exported to IBM SPSS v25 for analysis. Kruskal-Wallis H, Dunn-Bonferroni pairwise comparison test, and Spearman’s correlation analysis were used for inferential statistics. P Result The median and interquartile range of platelet count among combined oral contraceptive users was 285(238–332) which is significantly higher than that of depot medroxyprogesterone acetate users 246(220–226) (p = 0.010), implant user 247(221–297) (p = 0.034), and controls 256(224–278) (p = 0.015). The result also showed long-term use of implant negatively correlated with red blood cell count (p = 0.033). Conclusion This finding concludes that combined oral contraceptive users had a higher platelet counts than controls while long-term use of implants can result in low red blood cells count. Therefore, a baseline evaluation of complete blood count in women desiring contraceptive methods would also be recommended.