Background: Malignant diseases are usually associated with severe pain during their course especially at the end stages. Pancreatic head cancer is one of these diseases which can be associated with severe intolerable pains in the end stages. Sometimes, these pains are extremely severe and interfere with patient’s normal life. There are various techniques to control the pain out of which, celiac and splanchnic plexus blocks (temporary and permanent) are widely accepted procedures especially in severe cases and can control the pain efficiently. There are different approaches for performing this block which are all acceptable technically but are different in case of efficacy, accuracy and potential complications. Materials and Methods: Two groups were studied prospectively in 3 academic centers to evaluate different techniques of celiac plexus block in terms of feasibility and complications. For this purpose, 61 patients with a confirmed pancreatic head cancer who experienced severe pains were divided into two groups. CT- and sonographically-guided celiac and splanchnic plexus blocks were evaluated in group 1 (n=32) and group 2 (n=29), respectively. Results: This study showed that the pain control and patients’ satisfaction were greater in the CT-scan group (group A, p=0.18). The success rate of performing a ganglion block was higher in the ultrasound group (group B, p=0.000). The need for a re-block was also higher in the latter group. But, the quality of life improved more in the first group (CT-scan group). However, no statistically significant difference was found between the two groups regarding these two variables. Pain relief started earlier and lasted longer in the CT-scan group. No complication was detected except for one case of abdominal infection in the sonography group and in some cases a mild pain (score<3) was reported which was not significant. Conclusion: Considering the limited number of cases, it seems that although there was no significant difference in the outcome of plexus block or related complications between the two above-mentioned procedures, the suggested imaging technique for celiac plexus block is CT-scan because of its feasibility, accuracy and lower number of trials to achieve a favorable result. More complementary assessments are recommended to obtain more precise results. (Tanaffos 2009; 8(3): 51-57)