Background Primary sclerosing cholangitis (PSC) is a chronic progressive disease that primarily affects the medium and large biliary ducts. Methods This study investigated the baseline characteristics and predictors of clinical outcomes among hospitalized patients with PSC in the US. Using the National Inpatient Sample database from 2018 to 2020, we included adults with a principal diagnosis of PSC. Results Our study included 2585 adult hospitalizations. The prevalence of cirrhosis, ulcerative colitis (UC), Crohn’s disease (CD), and cholangiocarcinoma among hospitalized PSC patients was 44.5%, 32.3%, 13.15%, and 5.2%, respectively. Over a third of patients (38.1%) underwent endoscopic retrograde cholangiopancreatography (ERCP). UC, CD, cholangiocarcinoma, and autoimmune hepatitis had no impact on mortality, length of stay, or ERCP utilization. Interestingly, individuals of Asian/Pacific Islander ethnicity had higher odds of undergoing ERCP compared to White ethnicity (odds ratio 4.67, 95% confidence interval 1.25–17.4). Conversely, patients with cirrhosis and liver transplant recipients were less likely to undergo ERCP. Conclusion This is the first nationwide study to assess the clinical characteristics and outcomes of hospitalized patients with PSC. It highlights various factors associated with increased utilization of ERCP, longer length of stay, and increased inpatient mortality. Further research is warranted to explore these associations.