Background With the improvement in noninvasive diagnostic imaging modalities, Endoscopic Retrograde Cholangio-Pancreatography (ERCP) has evolved into a primarily therapeutic procedure. Besides being efficacious and one of the most commonly done procedures, ERCP is also associated with a high risk of complications. However, there is a lack of studies analyzing the safety and success of ERCP in patients with liver cirrhosis. We retrospectively evaluated the outcome of ERCP in patients with cirrhosis of the liver compared to non-cirrhotic patients using the database from our institute. Methods Patients with liver cirrhosis who underwent ERCP from January 2010 to March 2020 were analyzed. This was a matched case-control study in which one cirrhotic patient undergoing ERCP was age and gender-matched randomly to one non-cirrhotic patient. We compared adverse events and the success rate of ERCP between cirrhotic patients and non-cirrhotic patients. The primary outcome of the study was analyzing the prevalence of procedure-related adverse events and their independent risk factors in patients of cirrhosis compared to the non-cirrhotic population. Results Two hundred patients were analyzed in both groups. Choledocholithiasis was the most common reason for ERCP in both groups. Mean Child-Turcotte-Pugh (CTP) score and Model for End-stage Liver Disease (MELD) score in the cirrhosis group were 9.16 ±1.78 and 19.09 ±7.06 respectively. Patients in the cirrhosis group had a significantly higher frequency of complications compared to the controls: 41 (20.5 %) versus 15 (7.5%), p < 0.01. Bleeding was the most common adverse event in both groups: 19 (9.5%) vs 6(3%). High International Normalised Ratio (INR), low platelets, and cholangitis at presentation were independently predictive of post-ERCP complications. Despite a similar technical success rate, the clinical success rate was lower in the cirrhotic than in the noncirrhotic group (83.9% versus 97.9%, p=0.006). Conclusion The prevalence of complications following ERCP was nearly three-fold higher in patients with cirrhosis than in non-cirrhotic patients. These events were related primarily to cholangitis, coagulopathy, and the advanced status of chronic liver disease.