Previous meta-analyses of the effects of dietary cation anion difference (DCAD; mEq/kg; Na + K - Cl - S) in lactating dairy cow diets used studies conducted after the development of the DCAD concept. Dietary buffers, such as NaHCO3 and K2CO3, increase DCAD and have been used in lactating dairy cow diets for several decades. However, most published studies on buffer feeding were conducted before the development of the DCAD concept. Our objective was to determine the intake, milk production, ruminal, and feed efficiency responses to DCAD using previous studies with dietary buffer addition and more recent studies that focused on DCAD as dietary treatments. The database consisted of 43 articles that were published between 1965 and 2011. The studies included 196 dietary treatments and 89 treatment comparisons with a range in DCAD from -68 to 811mEq/kg of diet DM, with the vast majority between 0 and 500mEq/kg of diet DM. For studies that lacked analyses of one or more of the dietary strong ions (Na, K, Cl, or S), ion percentages were estimated from ingredient composition using the 2001 dairy National Research Council software. Two basic models were used to evaluate DCAD responses using the NLMIXED procedure in SAS 9.2 (SAS Institute Inc., Cary, NC): (1) a simple linear model, Y=A + B × (DCAD), where A=intercept and B=the increment (slope) in performance per unit DCAD (mEq/kg of diet DM); and (2) a nonlinear model, Y=A + M[1 - e((K × DCAD))], where M=maximal increment in performance from DCAD and K=the rate constant. In both models, study was designated as the random effect. The DCAD effects best described by the linear model included milk fat percent, fat yield, ruminal pH, NDF digestibility, and feed efficiency [3.5% fat-corrected milk (FCM; kg)/dry matter intake (DMI; kg)] where a 100mEq/kg increase in DCAD resulted in respective increases of 0.10%, 36g/d, 0.032 pH units, 1.5% NDF digestibility, and 0.013 FCM/DMI units. The DMI, milk yield, and 3.5% FCM were best described by the nonlinear model where the maximal responses were 1.92, 1.11, and 4.82kg/d, respectively. The expected increments in DMI, milk production, and 3.5% FCM by increasing DCAD from 0 to 500mEq/kg were 1.7, 1.2, and 3.4kg/cow per day, respectively. The results of this meta-analysis suggest that DCAD has significant effects on intake, milk production and composition, digestion, and feed efficiency in lactating dairy cows.