The objective of this study was to determine the effect of decreasing dietary cation-anion difference (DCAD) in the prepartum period on dry matter intake (DMI), milk production and milk composition. Multiparous Holstein cows (n = 89) were allocated randomly to one of 3 prepartum diets formulated with decreasing DCAD: CON (+17.5 mEq/100 g DM), MED (+3.6 mEq/100 g DM), or LOW (−10.9 mEq/100 g DM), beginning 24 d before expected parturition. Analyzed DCAD were +18.3, +5.9, and −7.4 mEq/100 g DM. Cows were fed a common postpartum diet from parturition until 63 d in milk. Repeated measures analyses were conducted using the MIXED procedure of SAS with linear and quadratic effects of decreasing prepartum DCAD as contrasts. A quadratic effect of decreasing DCAD on prepartum DMI was observed (CON = 14.6 kg/d, MED = 15.1 kg/d, LOW = 14.1 kg/d; P < 0.01). Postpartum DMI as a percent of body weight through wk 3 increased linearly with decreasing DCAD (CON = 2.94%, MED = 3.04%, LOW = 3.15%; P = 0.03) and tended to be increased through wk 9 (P = 0.07). During wk 1 to 3, milk yield (CON = 40.5 kg/d, MED = 42.1 kg/d, LOW = 43.8 kg/d; P = 0.03) and fat yield were increased linearly (P = 0.13) by decreasing prepartum DCAD resulting in a trend for greater 3.5% fat-corrected milk (P = 0.07). Protein percent decreased linearly (P < 0.01) with no effect on yield. Lactose yield (P = 0.02), total solids content (P = 0.01) and total solids yield (P = 0.06) were increased linearly, with a trend for greater energy-corrected milk for cows fed a lower DCAD (P = 0.08). Milk urea nitrogen increased linearly (P = 0.04) and there tended to be a quadratic effect on somatic cell score (P = 0.06). Effects of prepartum DCAD on milk yield and composition were smaller when assessed from wk 1 to 9. Cows fed lower prepartum DCAD had linearly decreased protein percent (P = 0.02) through wk 9 with a trend for a quadratic effect on yield (P = 0.11). Ultimately, there was no difference in fat or energy-corrected milk through wk 9. Feeding decreasing prepartum DCAD linearly increased DMI and milk yield during early lactation.