Background and aims: Pain is one of the consequences of chronic pancreatitis (CP) that has the greatest impact on the quality of life of patients. Endoscopic and surgical interventions, by producing a decrease in intraductal pancreatic pressure, can provide pain relief. This is the first systematic review that includes only randomized clinical trials (RTCs) comparing outcomes in the short-term (less than 2 years) and long-term (more than 2 years) between these two types of interventions. Material and methods: A comprehensive search of multiple electronic databases to identify RTCs comparing short and long-term pain relief, procedural complications, and days of hospitalization between endoscopic and surgical interventions was performed following the PRISMA guidelines. Results: Three RCTs evaluating a total of 199 patients (99 in the endoscopy group and 100 in the surgery group) were included in this study. Surgical interventions provided complete pain relief, with statistical difference, in the long-term (16,4% vs 35.7%; RD 0.19; 95% CI 0.03–0.35; p = 0.02; I2 = 0%), without significant difference in short-term (17.5% vs 31.2%; RD 0.14; 95% CI −0.01–0.28; p = 0.07; I2 = 0%) when compared to endoscopy. There was no statistical difference in short-term (17.5% vs 28.1%; RD 0.11; 95% CI −0.04–0.25; p = 0.15; I2 = 0%) and long-term (34% vs 41.1%; RD 0.07; 95% CI −0.10–0.24; p = 0.42; I2 0%) in partial relief of pain between both interventions. In the short-term, both complications (34.9% vs 29.7%; RD 0.05; 95% CI −0.10–0.21; p = 0.50; I2 = 48%) and days of hospitalization (MD −1.02; 95% CI −2.61–0.58; p = 0.21; I2 = 0%) showed no significant differences. Conclusion: Surgical interventions showed superior results when compared to endoscopy in terms of complete long-term pain relief. The number of complications and length of hospitalization in both groups were similar. [ABSTRACT FROM AUTHOR]