The objective of this study was to evaluate the efficacy of supplemental rumen-protected methionine (MET) and choline (CHO) on performance and health of transition cows. Eighty-one multiparous Holstein cows were used in a randomized complete block design with 2 × 2 factorial arrangement of MET (Smartamine M, Adisseo NA) and CHO (ReaShure, Balchem Inc.) level (with or without). Treatments (20–21 cows each) were control (CON), no MET or CHO; CON+MET (SMA); CON+CHO (REA); and CON+MET+CHO (MIX). From −50 d to −21 d before expected calving, all cows received the same diet (1.24 Mcal/kg DM) with no MET or CHO. From −21 d to calving, cows received the same close up diet (1.54 Mcal/kg DM) and were assigned randomly to treatments (CON, SMA, REA, or MIX). From calving to 30 DIM, cows were on the same postpartal diet (1.69 Mcal/kg DM) and continued to receive the same treatments through 30 DIM. MET supplementation was adjusted daily at 0.08% DM of diet and REA was supplemented at 60 g/cow/d. No differences (P = 0.34 or greater) were detected for pre- or postpartal body weight and body condition score. However, MET supplementation (SMA, MIX) led to greater (P < 0.05) DMI compared with other treatments (CON, REA) in both close-up (14.40 vs. 13.13 kg/d, SEM 0.40) and first 30 d postpartum (19.30 vs. 17.15 kg/d, SEM 0.63). Milk yield in MET-supplemented cows (SMA, MIX) also was greater (P < 0.05) compared with other (CON, REA) treatments (44.32 vs. 40.32 kg/d, SEM 1.29). Milk fat % did not differ in response to MET (P = 0.91; 3.72% vs. 3.74%, SEM 0.11%) or CHO (P = 0.46; 3.78% vs. 3.68%, SEM 0.10%). However, milk protein % was greater in MET-supplemented (P < 0.01; 3.32% vs. 3.14%, SEM 0.05%) but not CHO-supplemented (P = 0.23; 3.27% vs. 3.19%, SEM 0.05%) cows. CHO led to greater (P = 0.02) blood glucose. No MET or CHO effects were detected for blood NEFA (P = 0.56 or greater) or BHBA (P = 0.11 or greater), but a MET × time effect (P = 0.10) was observed for NEFA due to lower concentrations on d 4. Results from the present study indicate peripartal supplementation of rumen-protected methionine has positive effects on cow performance.