A meta-analysis of previous studies was performed to clarify the response of prepartum dairy cows to lowering dietary cation-anion difference (DCAD) and to compare different equations that have been proposed to calculate DCAD. Twenty-two published studies containing 75 treatment groups met criteria for inclusion in the meta-analysis. Five different equations used to calculate DCAD were compared for their association with clinical milk fever and urinary pH. The DCAD equation (Na + K) − (Cl + 0.6 S) was the most highly associated with clinical milk fever (R2 = 0.44) and urinary pH (R2 = 0.85). Lowering DCAD reduced clinical milk fever but also reduced DM intake. Lowered DCAD was associated with reduced urinary pH, blood bicarbonate, and blood CO2, suggesting a metabolic acidosis with respiratory compensation. Blood pH was very slightly lowered by lowered DCAD. Lowering DCAD increased ionized Ca in blood before and at calving. The model predicted that lowering DCAD from +300 to 0 mEq/kg reduced risk for clinical milk fever from 16.4 to 3.2%, reduced urinary pH from about 8.1 to 7.0, and reduced DM intake by 11.3%.