Betaine and choline were compared as supplementation strategies in fresh cow diets. Sixty multiparous cows at 14 d in milk were housed and randomly assigned to a treatment in a randomized design (4 cows per pen) across 15 pens. Supplements were control (CON), Reashure choline (CHOL, 55 g/cow/d), or betaine (BET, 25 g/cow/d) and were fed for 14 weeks. Cows were milked 3 times per day with daily individual milk yield averaged by week. Dry matter intake (DMI) per pen was averaged by week as well as individual milk composition was averaged by week (2 d average). Individual bodyweight and condition score occurred at initiation, d 28, d 70, and d 98 in lactation. Plasma concentrations of albumin, aspartate amino transferase, urea nitrogen (PUN), nonesterified fatty acids (NEFA), BHB, and haptoglobin were determined at d 0, d 28, and d 77. Proc GLIMMIX procedure of SAS with repeated measures over time was utilized to analyze the data. Differences were noted at P < 0.05 and trends at P < 0.15. The BET treatment reduced pen DMI compared with CON cows (25.35 vs 26.18 kg/d; P < 0.01) which led to higher milk fat (3.48 vs. 3.72%; P < 0.001) and lower milk protein percentage (2.89 vs. 2.83%; P < 0.02). These differences led to a similar ECM but greater 3.5 FCM yield over CON cows (53.84 vs. 55.42 kg/d; P < 0.001) for the BET treatment. Cows fed BET had greater 3.5 FCM (2.25 versus 2.10) and ECM (2.19 vs. 2.08) efficiencies (P < 0.001) over CON cows. The CHOL treatment increased milk yield (55.76 vs. 53.59 kg/d; P < 0.001), ECM yield (55.52 vs. 54.13 kg/d; P < 0.001), and elevated gross protein efficiency (35.27 vs. 34.18%) over BET. No differences were noted in initial or final body weight or condition as well as days to peak or peak milk yield. Choline lowered PUN levels (13.59 vs. 12.21 mg/dL) compared with CON and BET fed cows while BET increased NEFA (0.53 vs. 0.39 mEq/L) and BHB (8.91 vs. 7.03 mg/dL) levels compared with CON and CHOL fed cows. Choline appears to function via enhanced metabolism while betaine exerts an intake effect. More research is required to understand how to optimally feed betaine as well as to maximize choline inclusion.