To compare vascular enhancement, image quality, and radiation dose of 128-slice dual-source CT venography (CTV) between an imaging setting of 120 kVp with low pitch, and a setting of 100 kVp combined with high pitch and automatic tube current modulation. A total of 100 patients with suspected deep vein thrombosis and varicose veins were divided into two groups: Group 1 [50 patients, 120 kVp, low pitch (0.6), and fixed 120 mA) and Group 2 (50 patients, 100 kVp, high pitch (3.0), and automatic tube current modulation]. Two radiologists, who were blinded to the image protocol, assessed vascular enhancement and image noise in the inferior vena cava (IVC), femoral vein, and popliteal vein. They also assigned an image quality score independently using a 5-point visual scale. Effective dose was estimated using the dose-length product (DLP). Group demographics, radiation dose, vascular enhancement, image noise, and image quality in the two groups were analyzed. Mean vascular enhancement of the IVC, femoral vein, and popliteal vein was significantly higher in group 2 than in group 1, and images in group 2 had significantly higher image noise. However, there were no significant differences in subjective image quality score of the IVC, femoral vein, and popliteal vein. The mean DLP in group 2 (402.10 ± 94.29 mGy cm) was significantly lower than that in group 1 (973.36 ± 63.20 mGy cm) (P < 0.001). Lower extremity CTV using 100 kVp, high pitch (3.0), and automatic tube current modulation improved vascular enhancement with acceptable image quality and low radiation dose.