The biological half‐life of cadmium (Cd) is as long as 10–30 years. Exposure to this element induces renal tubular dysfunction, which is considered irreversible. β2‐microglobulin (β2‐MG) is a low‐molecular‐weight protein, and urinary β2‐MG is one of the most useful and critical indicators for the early detection of renal tubular dysfunction. However, very little research has been published concerning the long‐term observation of Cd‐induced adverse health effects. As such, this follow‐up study was conducted for 28 years to clarify the relationship between the concentration of Cd and β2‐MG in the urine of 28 inhabitants (14 male and 14 female) living in the Kakehashi River basin, Ishikawa prefecture (Japan), previously one of the most highly Cd‐polluted regions in this country. All subjects were over 60 years old in 2014 and participated in all six health examinations conducted over 28 years (1986–2014). Urine was collected at the appropriate time and kept frozen to analyze urinary Cd and β2‐MG concentrations. The urinary Cd concentration was found to decrease by nearly half between 1986 and 2008 in both male and female subjects, whereas it increased significantly from 2008 to 2014 in males. In contrast, urinary β2‐MG concentrations tended to increase over the 28‐year study period in both sexes. Urinary Cd and β2‐MG concentrations in females were significantly higher than those in males in this Cd‐polluted region. Age is more strongly associated with urinary β2‐MG concentration than recent Cd body burden. Copyright © 2016 John Wiley & Sons, Ltd. A follow‐up study was conducted over 28 years (1986–2014) to clarify the relationship between urinary cadmium (Cd) and β2‐microglobulin (β2‐MG) concentration in 28 inhabitants who lived in a previously Cd‐polluted region in Japan. Urinary Cd concentration decreased by nearly half in both sexes between 1986 and 2008. However, it increased significantly from 2008 to 2014 in males. Urinary β2‐MG concentrations tended to increase during the study. Age is more strongly associated with urinary β2‐MG concentration than recent Cd body burden.