Background: Extracorporeal shockwave is recommended as the first choice for the treatment of fracture nonunion, However, some patients with fracture nonunion have poor response to extracorporeal shockwave therapy. The present study aimed to investigate related factors which may affect the clinical efficacy of extracorporeal shockwave on fracture nonunion. Methods: Ultrasound examination was applied to observe nonunion gap, local blood supply, hardness of callus and hematoma formation before and after extracorporeal shockwave therapy. The patient's condition was followed up for 12 months after extracorporeal shockwave therapy. Four correlations and regression analysis methods were applied to analyze the factors which were correlated the clinical efficacy of extracorporeal shockwave. Receiver-operating characteristic analysis revealed that the cut-off of the fracture nonunion gap was 4.200 mm and the cut-off of the hardness of callus/impulse energy was 2.555. Single factor linear correlation analysis, multi-factor linear regression analysis, single-factor logistic regression analysis were applied. Results: The four ultrasound signs were significantly correlated with extracorporeal shockwave therapy: nonunion gap (r = -0.723; OR = 3.074), local blood supply (r = 0.611; OR = 0.191), hardness of callus/impulse energy (r = -0.510; OR = 19.942), and hematoma formation (r = 0.722; OR = 0.015). Conclusions: Nonunion gap larger than 4.200 mm and hardness of callus/impulse energy larger than 2.555 are risk factors of extracorporeal shockwave therapy outcome, and good local blood supply and effective hematoma formation induced by extracorporeal shockwave therapy are protective factors. By analyzing the related factors of extracorporeal shockwave therapy on fracture nonunion, clinicians may screen out the patients with fracture nonunion who are not suitable for extracorporeal shockwave therapy, and reduce the risk of fracture nonunion.