Background: Recently, the D-dimer biomarker has gained the researchers' attention for predicting infections. We aimed to determine the relationship between this marker and other inflammatory markers involved in orthopedic implant-associated infections. Materials and Methods: In this study, all patients diagnosed with an orthopedic implant-associated infection were investigated in 3 years. The serum level of D-dimer, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was measured. Infection was diagnosed based on the clinical and culture results of biopsy samples. Results: The cultured microorganisms, detected in 26 patients with infections, included Staphylococcus aureus (n = 13, 50%), Staphylococcus epidermidis (n = 2, 7.7%), Klebsiella aerogenes (n = 8, 30.8%), and Pseudomonas aeruginosa (n = 3, 11. 5%). Based on laboratory findings, there was a significant difference in the CRP level and ESR (P = 0.001). Although the level of D-dimer was higher in infected patients, compared to the controls (992.6 ± 667.2 vs. 690.1 ± 250.2 ng/mL), the difference was not statistically significant. There was no significant correlation between the elevated D-dimer level and CRP level, whereas ESR had a positive correlation with the elevated D-dimer level (r = 0.6, P = 0.03). The sensitivity, specificity, and positive predictive value (PPV) of D-dimer in the prediction of infection were 65%, 57%, and 45%, respectively. Furthermore, the sensitivity, specificity, and PPV of CRP were 100%, 92.3%, and 95%, respectively, whereas the corresponding values for ESR were 85%, 69.2%, and 62%, respectively. Conclusion: Measurement of the serum D-dimer level is not efficient for the diagnosis of orthopedic implant-associated infections due to its low predictive value. Furthermore, there was no significant correlation between the serum D-dimer level and CRP.