Objectives: Thick wall gallbladder (TWGB) is difficult to characterize on conventional imaging. Here we study the role of diffusion-weighted MRI in distinguishing between benign and malignant causes of TWGB. Methods: In this prospective study, we evaluated 25 patients with TWGB (__ampersandsigngt;3mm wall thickness) on ultrasound. Diffusion-weighted MRI was done with the calculation of apparent diffusion coefficient (ADC) values. Patients were subjected to an appropriate surgical procedure. MRI findings were compared with histopathological reports. Results: Mean age was 48.52__ampersandsignplusmn;9.6yrs (30-68yrs) with F: M ratio of 2.1:1. MRI showed diffusion restriction in 16 (64% patients), the breach in mucosal continuity in 13 (52%), and GB wall thickening in 20 (80%). MRI reported carcinoma in 12 (48%), cholecystitis in 11 (44%), and xanthogranulomatous cholecystitis (XC) in 2 (8%). Histopathology reports (available for 24 patients who were operated) revealed adenocarcinoma in 6, XC in 7, and cholecystitis in 11 patients. Diffusion restriction and absence of GB calculi were seen to be significantly related to malignancy. The sensitivity was 100% and specificity 88.9% for differentiating between carcinoma and cholecystitis. Overall, DWI-MRI had the sensitivity and negative predictive value of 100% each, the specificity of 66.67%, the positive predictive value of only 50%, and an accuracy of 75%. Conclusion: Diffusion-weighted MRI is a useful imaging modality for the characterization of thick wall GB when used with quantitative assessment of ADC values. It could help to diagnose the presence of malignancy in doubtful cases.