Purpose <p>Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease frequently associated with inflammatory bowel disease (IBD). While PSC with IBD is recognized as a distinct entity, comparative outcomes of PSC with IBD versus PSC alone remain uncertain. This systematic review and meta-analysis aimed to compare clinical outcomes in patients with PSC with and without comorbid IBD.</p> Methods <p>We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. MEDLINE, PubMed, Embase, Scopus, and CENTRAL were searched to October 2025. Eligible studies included adults with PSC stratified by IBD status, reporting risk of all-cause mortality or liver transplant, malignancy, graft survival, or recurrent PSC. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models.</p> Results <p>Twenty-six studies involving 23,837 patients (16,502 PSC-IBD; 7,335 PSC only) were included. PSC-IBD was associated with a significant decrease in all-cause mortality or liver transplantation compared with PSC alone (HR 0.77, 95% CI, 0.62—0.97). Subgroup analysis showed that both PSC with Crohn’s disease (HR 0.67, 95% CI 0.54—0.84) or ulcerative colitis (HR 0.72, 95% CI 0.55—0.95) had a significantly lower risk of all-cause mortality or liver transplantation compared to PSC alone. Indeterminate colitis carried a higher risk compared with Crohn’s disease (HR 1.57, 95% CI 1.00—2.4). PSC-IBD was associated with increased risk of hepatopancreatobiliary cancer (HR 2.37, 95% CI 1.35—4.15). There was no significant difference in risk of recurrent PSC between PSC-IBD and PSC only.</p> Conclusion <p>PSC-IBD may be associated with a lower risk of all-cause mortality and liver transplant compared to PSC alone, although these findings should be interpreted cautiously given the limited number of studies for several outcomes. Further prospective studies are needed to refine risk stratification.</p>