The role of water hardness on human health is still debated, ranging from beneficial to harmful. Before the rise of drinking bottled water, it was a common habit to obtain supplies of drinking water directly from spring-fed public fountains. According to the geographic location, spring waters are characterized by a variable content of mineral components. In this ecological study, for the first time in Sardinia, Italy, the spatial association between spring water quality/composition and standardized mortality ratio (SMR) for coronary artery disease (CAD) in the decade from 1981 to 1991 was investigated using data retrieved from published databases. In a total of 377 municipalities, 9918 deaths due to CAD, including acute myocardial infarction (AMI), ICD-9 code 410, and ischemic heart disease (IHD), ICD-9 code 411–414, were retrieved. A conditional autoregressive model with spatially structured random effects for each municipality was used. The average SMR for CAD in municipalities with a predominantly “soft” (<30 mg/L) or “hard” (≥30 mg/L) water was, respectively, 121.4 ± 59.1 vs. 104.7 ± 38.2 (p = 0.025). More specifically, an inverse association was found between elevated calcium content in spring water and cardiovascular mortality (AMI: r = −0.123, p = 0.032; IHD: r = −0.146, p = 0.009) and borderline significance for magnesium (AMI: r = −0.131, p = 0.054; IHD: r = −0.138, p = 0.074) and bicarbonate (IHD: r = −0.126, p = 0.058), whereas weak positive correlations were detected for sodium and chloride. The lowest CAD mortality was observed in geographic areas (North-West: SMR 0.92; South-East: SMR 0.88), where calcium- and bicarbonate-rich mineral waters were consumed. Our results, within the limitation of an ecological study, confirm the beneficial role of waters with high content in calcium and bicarbonate against coronary artery disease.