Abstract: Objective To investigate the relationship between serum epidermal growth factor-like repeats and discoidin I-like domain 3 (EDIL3), cell division cycle 42 (CDC42), and the prognosis of patients with type B aortic dissection (TBAD) undergoing endovascular aneurysm repair (EVAR). Methods A total of 135 TBAD patients who underwent EVAR in General Hospital of Hunan Medical University from January 2017 to January 2022 were selected and set a TBAD group. Meanwhile, 135 health examination volunteers were selected as a control group. According to the occurrence of aortic-related adverse events, TBAD patients were divided into two groups: good prognosis and poor prognosis. Serum EDIL3 and CDC42 levels were measured by enzyme-linked immunosorbent assay. LASSO regression was used to screen prognostic variables, and multivariate unconditional logistic regression was performed to analyze the relationship between EDIL3, CDC42 levels and prognosis. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of EDIL3 and CDC42 levels for adverse prognosis. Results Compared with the control group, serum EDIL3 and CDC42 levels in the TBAD group significantly decreased (P＜0.05). During the 2-year follow-up, the incidence of aortic-related adverse events after EVAR in TBAD patients was 35.56% (48/135). Serum EDIL3 and CDC42 levels in the poor prognosis group were significantly lower than those in the good prognosis group (P＜0.05). LASSO regression identified three non-zero characteristic variables: pleural effusion, EDIL3, and CDC42. EDIL3 and CDC42 were independent protective factors for EVAR prognosis (P＜0.05). The area under the ROC curve (AUC) for combined EDIL3 and CDC42 prediction of adverse prognosis was 0.872, which was significantly higher than that of EDIL3 (0.789) or CDC42 (0.778) alone (P＜0.05). Conclusions Decreased serum EDIL3 and CDC42 levels are closely associated with poor prognosis in TBAD patients after EVAR. The combined detection of EDIL3 and CDC42 provides high predictive efficiency for adverse outcomes.