In the diagnosis of chronic pancreatitis (CP), definition of main pancreatic duct (MPD) dilation is challenging due to lack of commonly accepted normal values. This study assessed the diagnostic performance of MPD diameters to detect CP including the impact of age. 274 patients with ERCP-verified CP and 262 healthy controls were included. All had magnetic resonance cholangiopancreatography (MRCP) with measurement of MPD diameters in the pancreatic head, body, and tail. CP disease stage was defined as patients with and without functional (exocrine and/or endocrine) impairment. Diagnostic performance of MPD diameter and corresponding cut-offs values to diagnose CP were determined, including an age-stratified analysis. In healthy controls, an effect of age on MPD diameters was seen for the pancreatic head (P < 0.001), body (P = 0.006), and tail (P = 0.03). Patients with CP had increased MPD diameter compared to controls (all segments P < 0.001). Increased pancreatic head MPD diameter was seen in patients with functional pancreatic impairment compared to patients without (P = 0.03). The diagnostic performance of MPD diameter to detect CP was high (all segments ROC-AUC > 0.92). The optimal pancreatic MPD diameter cut-off values for diagnosing CP were: < 40 years: 2.0(head) and 1.8(body) mm; 40–60 years: 2.4(head) and 2.1(body) mm; > 60 years: 2.7(head) and 2.1(body) mm. Age is an important factor when evaluating the diameter of the pancreatic ductal system. Our findings challenge the existing reported thresholds for defining an abnormal duct diameter and point at age-stratified assessments as an integrated part of future imaging-based diagnostic and grading systems for CP.