Objective To evaluate the safety and feasibility of double endoscopic bypass, namely endoscopic ultrasound-guided gastroenterostomy (EUS-GE) combined with endoscopic ultrasound-guided biliary drainage (EUS-BD), for malignant gastric outlet and biliary obstruction. Methods A retrospective analysis was conducted on data of 10 patients with malignant gastric outlet and biliary obstruction who were not suitable for surgery or endoscopic retrograde cholangiopancreatography (ERCP) and treated by double endoscopic bypass in Nanjing Drum Tower Hospital from August 2017 to October 2020. The completion of therapy, clinical efficacy and post-procedure adverse events were analyzed. Results Ten patients with different malignant cancer successfully underwent EUS-GE and EUS-BD, with procedure time of 60.5±22.3 min (30-100 min). There were no postoperative adverse events. EUS-GE was clinically successful in all 10 cases. Of the 10 EUS-BD cases, 9 were clinically successful, and 1 did not meet the criteria of clinical success. The median follow-up was 71 (37-120) days. None of the 10 patients had recurrent gastric outflow tract obstruction or biliary tract obstruction. Conclusion Double endoscopic bypass is feasible and effective for patients with malignant gastric outlet and biliary obstruction and without surgery or ERCP opportunity.