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(1) Background: The combination of candidate selection, immunosuppressive therapy adjustment, and scrutinous monitoring is a cornerstone for optimizing long-term survival after a heart transplant. Neutrophil-to-lymphocyte ratio (NLR) is a simple marker of inflammatory reactions activation and may play a clinical role as a predictive marker in oncological and cardiovascular diseases. The aim of the study was to find simple hematologic indices available from whole blood count to help in immunosuppressive therapy monitoring. (2) Methods: Thirty patients (23 men and 7 women) with a mean age of 43 +/− 13 years who had undergone orthotopic heart transplantation were enrolled into the study. The blood samples for whole blood count and Tacrolimus level were collected during outpatient visits in heart transplant recipients every two months for 18 months after first year post transplantation. (3) Results: There was a significant correlation between Tacrolimus overdose (>15 ng/mL) and NLR (Spearman's rho 0.99, p < 0.001) and mean platelet volume (Spearman's rho 0.989, p < 0.001). The ROC analysis for NLR above 3.62 showed predictive properties for Tacrolimus overdose (over 15 ng/mL) (AUC =0.633, p = 0.008) with a sensitivity of 50% and specificity of 83.73%. (4) Conclusions: Our results suggest that NLR above 3.62 may be regarded as a simple indicator of tacrolimus overdose. [ABSTRACT FROM AUTHOR]