The aim of this study was to retrospectively measure and compare pancreatic apparent diffusion coefficient (ADC) in patients with acute pancreatitis (AP) with aged matched controls who underwent diffusion weighted imaging (DWI). The institutional review board approved this retrospective Health Insurance Portability and Accountability Act compliant study with a waiver for informed consent. Pancreatic ADC values from 27 patients with a clinical diagnosis of AP and 38 normal age-matched controls evaluated with DWI (b = 0 and 800 mm(2)/s) were retrospectively and independently measured by two radiologists. The ADCs were compared between the groups and between each of the pancreatic segments in the normal group. Inter-observer reliability was calculated and receiver operating characteristic analysis was used to determine the sensitivity and specificity of DW imaging in the diagnosis of acute pancreatitis. P < 0.05 was considered statistically significant. The ICC for inter-observer reliability was 0.98 in the control and 0.97 in the AP group. The mean pancreatic ADC in the AP group (1.32 × 10(-3) mm(2)/s ± 0.13) was significantly lower than in the normal group (1.77 × 10(-3) mm(2)/s ± 0.32). There was no significant difference in mean ADCs between each of the pancreatic segments in the controls. A threshold ADC value of 1.62 × 10-3 mm(2)/s yielded a sensitivity of 93% and specificity of 87% for detecting acute pancreatitis for b values of 0 and 800 s/mm(2). Pancreatic ADCs are significantly lower in patients with AP than normal controls.