Objective To compare the effects of contrast medium with two different iodine concentrations (iopamidol 300 mgI/mL and 370 mgI/mL) on the conspicuity of hypervascular hepatocellular carcinoma (HCC) during dual-energy CT (DECT) of the liver, use of a protocol with iodine dose adjusted for the patient’s body surface area (BSA, 17.1 gI/m2 BSA) and fixed injection duration (25s). Methods 300 patients were prospectively randomized into two groups. Patients in group A received iopamidol with an iodine concentration of 300 mgI/ml, B received iopamidol with an iodine concentration of 370 mgI/ml respectively. Iodine dose was adjusted according to BSA, with a fixed injection duration of 25 s. Sixty-eight patients had 83 hypervascular HCCs. Dual-energy acquisition mode was performed during late hepatic-arterial phase. Image quality and the tumor-to-liver contrast-to-noise ratio (TLCNR) were compared between higher-concentration contrast medium and lower-concentration contrast medium at 80- and 140-kVp and color iodine overlay images. Resutlts Mean TLCNR at 80 kVp were (3.46±1.41) for group A and (2.97±1.14) for group B (P=0.08); mean TLCNR at 140 kVp were (0.89±0.75) for group A and 0.87±0.70 for group B (P=0.92), mean TLCNR at color iodine overlay images were (5.21±1.93) for group A and (5.49±2.21) for group B (P=0.53). Quantitative analysis did not show significant differences between groups (P>0.05) at At 80- or 140-kVp or color iodine overlay images. Conclusion With fixed injection duration (25 s) and iodine load being tailored according to BSA, comparable conspicuity of hypervascular HCC can be achieved with 300 mgI/ml and 370 mgI/ml being injected at contrast-enhanced DECT imaging of the liver.