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Objectives: Endoscopic ultrasound (EUS) or percutaneous‐assisted antegrade guidewire insertion can be used to achieve biliary access when standard endoscopic retrograde cholangiopancreatography (ERCP) fails. We conducted a systematic review and meta‐analysis to evaluate and compare the effectiveness and safety of EUS‐assisted rendezvous (EUS‐RV) and percutaneous rendezvous (PERC‐RV) ERCP. Methods: We searched multiple databases from inception to September 2022 to identify studies reporting on EUS‐RV and PERC‐RV in failed ERCP. A random‐effects model was used to summarize the pooled rates of technical success and adverse events with 95% confidence interval (CI). Results: In total, 524 patients (19 studies) and 591 patients (12 studies) were managed by EUS‐RV and PERC‐RV, respectively. The pooled technical successes were 88.7% (95% CI 84.6–92.8%, I2 = 70.5%) for EUS‐RV and 94.1% (95% CI 91.1–97.1%, I2 = 59.2%) for PERC‐RV (P = 0.088). The technical success rates of EUS‐RV and PERC‐RV were comparable in subgroups of benign diseases (89.2% vs. 95.8%, P = 0.068), malignant diseases (90.3% vs. 95.5%, P = 0.193), and normal anatomy (90.7% vs. 95.9%, P = 0.240). However, patients with surgically altered anatomy had poorer technical success after EUS‐RV than after PERC‐RV (58.7% vs. 93.1%, P = 0.036). The pooled rates of overall adverse events were 9.8% for EUS‐RV and 13.4% for PERC‐RV (P = 0.686). Conclusions: Both EUS‐RV and PERC‐RV have exhibited high technical success rates. When standard ERCP fails, EUS‐RV and PERC‐RV are comparably effective rescue techniques if adequate expertise and facilities are feasible. However, in patients with surgically altered anatomy, PERC‐RV might be the preferred choice over EUS‐RV because of its higher technical success rate. [ABSTRACT FROM AUTHOR]