Research indicates that lactating dairy cows have a requirement for metabolizable lysine (MP Lys). Porcine blood meal (PBM) is a common, but highly inconsistent source of MP Lys in dairy diets. The study objective was to determine the efficacy of a rumen-protected lysine product (USA Lysine, Kemin Industries, Inc., Des Moines, IA) as a source of MP Lys in diets fed to early lactation Holstein cows compared with PBM. Thirty cows (8 primiparous and 22 multiparous; average 121, range 45–175 DIM) were utilized in a trial consisting of a 2-wk covariate period, a 4-wk treatment period (period 1), a 1-wk washout period and a 4-wk treatment period (period 2). At the end of the covariate, cows were blocked by parity, DIM and milk yield, then randomly assigned to 1 of 2 treatment sequences (n = 15) according to a crossover design. There were 2 diets: 1) Control (CON) - PBM as the main source of MP Lys; and 2) USA Lysine (USA-L) - USA Lysine with dried distillers grains w/ solubles (DDGS) replacing most the PBM. Cows were individually fed 1×/d and milked 2×/d. Milk yield and dry matter intake (DMI) were recorded daily and milk components were determined weekly. Data were analyzed with the Mixed procedure of SAS (SAS Institute, Inc. Cary, NC). The model included the fixed effects of treatment, period, week in period (as a repeated measure), sequence, parity, treatment by week in period, treatment by parity and the random effect of cow nested within sequence. Significance was declared at P < 0.05 and tendencies at 0.05 < P < 0.10. There were no differences (P > 0.25) between the CON and USA-L treatment groups in DMI (25.90 vs. 25.63 kg/h/d) or milk yield (41.71 vs. 41.19 kg/h/d), respectively. Milk components and component yields, as well as feed efficiency, were nearly identical across treatments. Nitrogen use efficiency in terms of milk urea nitrogen (MUN) was improved with the USA-L diet (9.98 vs. 10.74 mg/dL, P < 0.01) compared with the CON diet. In conclusion, USA Lysine in combination with DDGS effectively replaced PBM as the main source of MP Lys in a diet formulated for high-producing Holstein dairy cows.