Purpose: To evaluate the diagnostic performance and interrater reliability of the Liver Imaging Reporting and Data System (LI-RADS) version 2014 in differentiating hepatocellular carcinoma (HCC) from non- HCC malignancy in a population of patients at risk for HCC. Materials and Methods: This retrospective HIPAA-compliant institutional review board-approved study was exempt from informed consent. A total of 178 pathology-proven malignant liver masses were identified in 178 patients at risk for HCC but without established extrahepatic malignancy from August 2012 through August 2015. Two readers blinded to pathology findings and clinical follow-up data independently evaluated a liver protocol magnetic resonance or computed tomography study for each lesion and assigned LI-RADS categories, scoring all major and most ancillary features. Statistical analyses included the independent samples t test, x2 test, Fisher exact test, and Cohen k. Results: This study included 136 HCCs and 42 non-HCC malignancies. Specificity and positive predictive value of an HCC imaging diagnosis (LR-5 or LR-5V) were 69.0% and 90.5%, respectively, for reader 1 (R1) and 88.3% and 95.5%, respectively, for reader 2 (R2). Tumor in vein was a common finding in patients with non- HCC malignancies (R1, 10 of 42 [23.8%]; R2, five of 42 [11.9%]). Exclusion of the LR-5V pathway improved specificity and positive predictive value for HCC to 83.3% and 92.9%, respectively, for R1 (six fewer false-positive findings) and 92.3% and 96.4%, respectively, for R2 (one fewer false-positive finding). Among masses with arterial phase hyperenhancement, the rim pattern was more common among non-HCC malignancies than among HCCs for both readers (R1: 24 of 36 [66.7%] vs 13 of 124, [10.5%], P < .001; R2: 27 of 35 [77.1%] vs 21 of 123 [17.1%], P < .001) (k = 0.76). Exclusion of rim arterial phase hyperenhancement as a means of satisfying LR-5 criteria also improved specificity and positive predictive value for HCC (R1, two fewer false-positive findings). Conclusion: Modification of the algorithmic role of tumor in vein and rim arterial phase hyperenhancement improves the diagnostic performance of LI-RADS version 2014 in differentiating HCC from non-HCC malignancy.