To evaluate the role of tissue harmonic imaging (THI) in acute pancreatitis, and to compare its findings with conventional grey-scale sonography and contrast-enhanced computed tomography (CECT) scan, we evaluated 25 patients diagnosed with acute pancreatitis on clinical examination and laboratory findings. Conventional grey-scale ultrasound followed by tissue harmonic sonography was done on the same machine followed by a CECT within 12 h of the ultrasound examination. The present study showed that sonograms obtained with THI were of much better quality than those obtained conventionally, especially for the pancreatic tail. The benefits of harmonic imaging were more apparent in obese patients and in others whose body habitus was unfavourable for sonography. In the assessment of pancreatic image quality, grey-scale imaging had an accuracy of 60, 80 and 28% in relation to the head, body and tail, respectively. In comparison, THI had a far higher accuracy of 80, 92 and 60% in relation to the head, body and tail, respectively, with the superiority being most obvious in the pancreatic tail region. There were no cases in which tissue harmonic sonography provided less information than conventional sonography. However, CECT scan remained the best modality in all patients for the evaluation of acute pancreatitis. It showed superior demonstration of all the morphological changes, ranging from minimal pancreatic oedema to extensive fluid collections, necrosis and the haemorrhage that developed in fulminant severe pancreatitis. Our experience thus suggests that THI cannot replace CT scan as the gold standard in the assessment of acute pancreatitis, as it is poor in evaluating the pancreatic tail, cannot clearly distinguish phlegmon from necrosis, and is inferior to CT in the assessment of the complications of acute pancreatitis.