The activated partial thromboplastin time (APTT) assay is essential for evaluating coagulation. However, prolonged APTT may result from pathological conditions or contamination with unfractionated heparin (UFH), which can occur due to improper phlebotomy or use of heparinized lines—even in patients not on UFH therapy. Distinguishing between true pathology and heparin contamination is critical for patient care and appropriate laboratory reporting. This study assessed the effectiveness of Antihepca HRRS (AHCa, a Heparin Resistant Recalcifying Solution (HRRS)), in neutralizing heparin interference in APTT testing. APTT results using AHCa HRRS and standard 0.025 M CaCl₂ were compared in 33 heparinized and 41 non-heparinized patient samples on Sysmex CN-6000 and Stago Start Max analyzers. Additionally, 30 random plasma samples with prolonged APTT were tested, and heparin-spiked plasmas were used to determine AHCa HRRS’s neutralization limit. AHCa HRRS fully corrected prolonged APTT in samples containing up to 0.6 IU/mL UFH. In the 33 heparinized samples, AHCa HRRS reduced all APTT results to <40 s, eliminating the need for urgent reporting. Among the 30 prolonged APTT samples, 8 were corrected by AHCa HRRS (indicating heparin), 20 remained prolonged (suggesting other causes), and 1 was inconclusive. In non-heparinized samples, AHCa HRRS caused only minor APTT shortening (∼5%), confirming minimal impact on true results. Overall, AHCa HRRS effectively neutralizes UFH interference in APTT testing without compromising accuracy in non-heparinized samples. It offers a practical alternative to conventional calcium reagents and thrombin time for identifying heparin contamination in clinical laboratories.