Background Acute ascending cholangitis is a life-threatening infection due to biliary obstruction. Decompression via endoscopic retrograde cholangiography (ERC) or interventional radiologic (IR) drainage controls the source of the sepsis. Numerous studies have been published with conflicting data on whether earlier drainage affects morbidity and mortality. We sought to publish our experience at two Las Vegas community hospitals. Methods After IRB approval, over 4000 inpatient non-elective ERCs were analyzed between 2010 and 2019. Six-hundred and twenty-five patients met the 2018 Tokyo criteria for a “definitive diagnosis” of acute ascending cholangitis. A univariate and multivariate analysis was conducted to identify factors significantly associated with length of stay and mortality. Results On univariate analysis, patients who had drainage conducted within 24 hours had significantly shorter lengths of stay (p = 0.0012 95% CI [-88.1 to -21.8 hrs]), higher mean diastolic blood pressure (p=0.0029 95% CI [1.03 to 5.01 mm Hg]), and lower mean maximum temperature (p=0.0001 95% CI [-0.842 to -0.382 o C]) when compared to patients who underwent decompression more than 24 hours after admission. There were no statistically significant differences in mortality between patients who underwent decompression within 24 hours of admission versus patients who underwent decompression beyond 24 hours of admission. On multivariate analysis, earlier decompression reduced the length of stay for patients with mild (p<0.0001), moderate (p<0.0001), and severe cholangitis (p=0.0023). Mortality was significantly associated with the worsening severity of the cholangitis (moderate [p=0.0001] and severe [p<0.0001], but not mild disease) and the use of vasopressors. Conclusions Timely biliary decompression within 24 hours of admission significantly reduces the length of stay, pyrexia, and hemodynamic abnormalities. In addition, our data corroborate the 2018 Tokyo guidelines that correlate the severity of cholangitis with mortality.