Introduction and objective: Colonic wall thickening is a common condition in a number of benignant and malignant diseases. This study investigated the accuracy of radiological diagnoses in patients diagnosed with colonic wall thickening using multislice CT (MDCT). Materials and Method: Files of patients with colonic wall thickening diagnosed with 64-slice MDCT were reviewed retrospectively. The colonoscopy results of these patients were grouped under neoplastic process (cancer and adenomatous polyp), inflammatory bowel disease (IBD), diverticulitis and other etiology (nonspecific events, ischemic colitis, solitary rectal ulcer, external compression, secondary to volvulus and radiotherapy), and the results were statistically evaluated. p values < 0.05 were considered statistically significant. Results: The study was performed on 505 files (290 males [57.4%], 215 females [42.6%], mean age: 49.15 +/- 18.4 years). CT and colonoscopic diagnoses were reviewed and the following CT to colonoscopy ratios was observed: neoplastic process: 44.4% vs. 40.2%; IBD: 42.4% vs. 42.4%; diverticulitis: 4% vs. 4.2%; other etiology: 9.3% vs. 3.2%. Colonoscopy failed to identify pathology in 9.9% of the patients. The sensitivity, specificity, PPV, NPV and accuracy of CT were 95.6%, 90.4%, 87.1%, 96.8% and 92.4%, respectively, in detecting neoplastic processes; 97.2%, 97.9%, 97.2%, 97.9% and 97.6%, respectively, in detecting IBD; 90.5%, 99.8%, 95%, 99.6% and 99.4%, respectively, in detecting diverticulitis, and 50%, 96,7%, 62.5%, 94.6% and 92%, respectively, in detecting other etiology. Conclusion: While, accuracy of 64 slice-CT in diagnosing colonic wall thickenings secondary especially to neoplastic processes, IBD and diverticulitis was significantly higher, but differential diagnosis is challenging in pathologies due to other etiologies.