ObjectivesEndoscopic vacuum therapy (EVT) possesses a unique mechanism of action providing a less invasive alternative for the management of transmural gastrointestinal defects (TGID). This study evaluates the efficacy and safety of a novel homemade EVT (H‐EVT) for the treatment of TGID.MethodsRetrospective multicenter study including patients who underwent H‐EVT for TGID between January 2019 and January 2022. Main outcomes included technical and clinical success as well as safety outcomes. Subgroup analyses were included by defect location and classification. Logistic regression analyses were performed to determine predictors for successful closure.ResultsA total of 144 patients were included. Technical success was achieved in all patients, with clinical success achieved in 88.89% after a mean of 3.49 H‐EVT exchanges over an average of 23.51 days. After excluding 10 cases wherein it was not possible to achieve negative pressure, successful closure occurred in 95.52% of patients. Time to clinical success was less for defects caused by endoscopic (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.33–1.20) compared to surgical procedures and for patients with simultaneous intracavitary and intraluminal H‐EVT placement (HR 0.70; 95% CI 0.55–0.91). Location and classification of defect did not impact clinical success rate. Simultaneous placement of both an intraluminal and intracavitary H‐EVT (odds ratio 3.08; 95% CI 1.19–7.95) was a significant predictor of clinical success. Three device‐related adverse events (2.08%) occurred.ConclusionsThe use of the H‐EVT is feasible, safe, and effective for the management of TGID.