Screening programmes for cirrhotic patients are based on ultrasound (US) examinations at 6-month intervals, but a US sensitivity of 47% has recently been reported. The aim of this study was to evaluate a two-phase MDCT protocol in terms of hepatic nodule detection within a hepatocellular carcinoma (HCC) screening situation and to evaluate a reduction in irradiation dose for the 6-monthly checks compared to the classic four-phase protocol. In total, 373 patients with 498 nodules that were suspected to be HCC and ranged from 10 to 30 mm in size were prospectively included. All patients underwent four-phase MDCT with an unenhanced phase, arterial phase (AP), portal phase (PP) and delayed phase (DP). The cumulative irradiation from the repeated 6-monthly MDCT protocol was calculated. Of the 498 nodules, only 4 (0.008%) were only seen in the PP and not in the AP or AP. Of the 319 HCC nodules, 270 (84.6%) had AP hyperenhancement, while 115 had washout in the PP and 224 had washout in the DP. Overall, 222 of the 224 (99.1%) HCC nodules with typical features were seen in the AP and DP. The dose reduction was estimated at 55.4% when using the two-phase protocol (AP and DP). The cumulative irradiation of the two-phase protocol, which was performed every 6 months over 5 years, was 96.5 mSv. MDCT with the two-phase protocol could offer an alternative to ultrasound screening with an interesting risk–benefit trade-off.