Protein C global is a global dotting assay that evaluates abnormalities in the protein C anticoagulant pathway. A few studies have examined this assay in relation to assisted reproductive technology (ART), but its role in infertile women with in vitro fertilization (IVF) failure remains unclear. In this study, we assessed protein C in infertile women with a history of IVF failure who were undergoing ART. We examined 45 healthy fertile women who conceived naturally, and 45 infertile women with 2 or more implantation failures undergoing ART. Both protein C and activated protein C resistance (APC-R) were evaluated. The results showed that mean protein C expressed as a normalized ratio (PCAT-NR) was significantly lower in the study group compared to the control group (0.76 ± 0.15 vs. 0.91 ± 0.14, respectively; p = 0.0001). Follow-up on ART outcomes showed that women who failed ART had significantly lower PCAT-NR compared to successful cases. PCAT-NR did not correlate with APC-R levels in the study (r = 0.125, p < 0.5) or failed ART subgroups. Using logistic regression analysis, patients with lower PCAT-NR levels showed an elevated risk of implantation failure (p = 0.04, OR 0.50, 95% CI 0.26-0.84). In conclusion, protein C global assay may play a role in the etiology of IVF failure, which might be independent of APC-R. Larger studies are encouraged to validate these findings and explore the underlying pathophysiological mechanisms.