Background/Aims: Biliary cannulation is a critical component of endoscopic retrograde cholangiopancreatography (ERCP). When standard methods fail, needle-knife precut sphincterotomy (NKPS) is commonly employed. This systematic review and meta-analysis evaluated the safety and efficacy of using NKPS as a primary technique. Methods: Electronic databases were searched for studies published between January 2000 and November 2024 that assessed outcomes of primary precut techniques. “Primary precut” was defined as needle-knife sphincterotomy performed as the initial approach without any prior standard cannulation attempts. Pooled proportions were calculated using random-effects models, and heterogeneity was assessed using the Q-test and the I² statistic. Results: The mean patient age was 57.95 years (standard deviation [SD], 7.59), and 53.23% were female. The cannulation success rate was 96.50% (95% confidence interval [CI], 94.90–97.60) with no heterogeneity (Q, 7.10; df, 8; I²=0%; p=0.935). The rates of adverse events were as follows: post-ERCP pancreatitis, 1.90% (95% CI, 1.20–3.10; I²=0; p =0.942); bleeding, 2.60% (95% CI, 1.70–4.00, I²=0; p=0.725); cholangitis, 1.50% (95% CI, 0.60–3.60; I²=45.27; p=0.067); and perforation, 0.90% (95% CI, 0.40–1.90; I²=0; p=0.948). The overall adverse event rate was 9.70% (95% CI, 5.70–16.10; I²=83.39; p<0.001). Conclusions Primary precut sphincterotomy appears to be an effective and safe technique for biliary cannulation in ERCP. These findings support its consideration as a viable first-line approach in appropriate clinical settings.