Background: Hepatocellular carcinoma (HCC) can be diagnosed using imaging criteria in patients at high-risk for HCC, according to Liver Imaging Reporting and Data System (LI-RADS) guidelines. The aim of this study was to determine the diagnostic performance and inter-rater reliability (IRR) of LI-RADS v2018 for differentiating HCC from non-HCC primary liver carcinoma (PLC), in patients who are at increased risk for HCC but not included in the LI-RADS ‘high-risk’ population. Methods: This retrospective HIPAA-compliant study included a 10-year experience of pathologically-proven PLC at two liver transplant centers, and included patients with non-cirrhotic hepatitis C infection, non-cirrhotic non-alcoholic fatty liver disease, and fibrosis. Two readers evaluated each lesion and assigned an overall LI-RADS diagnostic category, additionally scoring all major, LR-M, and ancillary features. Results: The final study cohort consisted of 27 HCCs and 104 non-HCC PLC in 131 patients. The specificity of a ‘definite HCC’ designation was 97% for reader 1 and 100% for reader 2. The IRR was fair for overall LI-RADS category and substantial for most major features. Conclusion: In a population at increased risk for HCC but not currently included in the LI-RADS ‘high-risk’ population, LI-RADS v2018 demonstrated very high specificity for distinguishing pathologically-proven HCC from non-HCC PLC.