Incidence of subclinical hypocalcemia in early postpartum dairy cows continues to be an animal welfare concern and an economic burden for producers. Feeding negative dietary cation-anion difference (DCAD) diets produces metabolic acidosis which mobilizes bone calcium and reduces the incidence of hypocalcemia. Achieving a sufficient degree of metabolic acidosis without reducing DMI is a challenge. This study compared the ability of MegAnion^® (MA), a new DCAD supplement designed to be more palatable than typical anionic salts, and another palatable commercial chloride (CC) source to create metabolic acidosis without reducing DMI. Prepartum Holstein (HO) and crossbred (XX) cows were blocked by breed and expected calving date and randomly assigned within breed to TMR formulated with MA or CC to have DCAD = -215 mEq/kg DM. Cows (N = 56; 15 MA-HO, 12 CC-HO, 15 MA-XX, 14 CC-XX) consumed the TMR for at least 19 d and completed the 28 d DIM phase of the study. Urine and blood samples were collected weekly and at 1, 2 and 3 DIM. Data were analyzed as a randomized block design by repeated measures (PROC MIXED) with week or DIM as the repeated effect. Prepartum urine pH decreased from 8.2 ± 0.27 prior to treatment to 6.1 ± 0.13 while treated, was not affected by diet (P = 0.60) and increased immediately after calving when all cows consumed the same TMR. Pre- (P > 0.17) and post- (P > 0.40) partum production variables (BW, BCS, DMI, energy balance, milk yield) were not affected by treatment but 3.5% FCM yield was greater in HO than XX cows (45.7 vs 41.0 ± 1.9 kg/d; P = 0.037). Prepartum serum calcium was not affected (9.3 mg/dL, P = 0.59) by treatment while non-esterified fatty acids were lower (86 vs 120 ± 10 µEq/L, P = 0.015) and insulin greater (31 vs 25 ± 1.5 ng/ml, P = 0.002) in MA than CC. These differences are supported by the numerical increases in prepartum DMI (1.2 kg/d, P = 0.17) and energy balance (1.8 Mcal/d, P = 0.19) of cows fed MA. Results indicate MA is a palatable and effective option for producers to induce prepartum metabolic acidosis to minimize hypocalcemia in dairy cows.