An area with extremely high incidence of urinary calculi was investigated in the view of identifying the relationship between the disease prevalence and the drinking water geochemistry. The prevalence of the kidney stone disease in the selected Padiyapelella-Hanguranketa area in Central Highlands of Sri Lanka is significantly higher compared with neighboring regions. Drinking water samples were collected from water sources that used by clinically identified kidney stone patients and healthy people. A total of 83 samples were collected and analyzed for major anions and cations. The anions in the area varied in the order HCO3 (-) > Cl(-) > SO4 (2-) > NO3 (-) and cations varied in the order Ca(2+) > Mg(2+) > Na(+) > K(+) > Fe(2+). The dissolved silica that occurs as silicic acid (H4SiO4) in natural waters varied from 8.8 to 84 mg/L in prevalence samples, while it was between 9.7 and 65 mg/L for samples from non-prevalence locations. Hydrogeochemical data obtained from the two groups were compared using the Wilcoxon rank-sum test. It showed that pH, total hardness, Na(+), Ca(2+) and Fe(2+) had significant difference (p < 0.005) between water sources used by patients and non-patients. Elemental ratio plots, Gibbs' plot and factor analysis indicated that the chemical composition of water sources in this area is strongly influenced by rock-water interactions, particularly the weathering of carbonate and silicate minerals. This study reveals a kind of association between stone formation and drinking water geochemistry as evident by the high hardness/calcium contents in spring water used by patients.