Objective: Our objective was to examine the relationships of supplemental rumen-protected lysine (RPL) or lysine + methionine (RPLM) on lactational performance, plasma amino acids (AA) concentration, and nitrogen use efficiency of lactating dairy cows by using a meta-analysis approach.Methods: A total of 56 articles comprising 77 experiments with either RPL or RPLM supplementation were selected and analyzed using a mixed model methodology by considering the treatments and other potential covariates as fixed effects and different experiments as random effects.Results: In early lactating cows, milk yield was linearly increased by RPL (β<sub>1</sub> = 0.013; p<0.001) and RPLM (β<sub>1</sub> = 0.014; p<0.028) but 3.5% fat-corrected milk (FCM) and energy-corrected milk (ECM) (kg/d) was increased by only RPL. RPL and RPLM did not affect dry matter intake (DMI) but positively increased (p<0.05) dairy efficiency (Milk yield/DMI and ECM/DMI). As a percentage, milk fat, protein, and lactose were unchanged by RPL or RPLM but the yield of all components was increased (p<0.05) by feeding RPL while only milk protein was increased by feeding RPLM. Plasma Lys concentration was linearly increased (p<0.05) with increasing supplemental RPL while plasma Met increased (p<0.05) by RPLM supplementation. The increase in plasma Lys had a strong linear relationship (<i>R</i><sup>2</sup> = 0.693 in the RPL dataset and <i>R</i><sup>2</sup> = 0.769 in the RPLM dataset) on milk protein synthesis (g/d) during early lactation. Nitrogen metabolism parameters were not affected by feeding RPL or RPLM, either top-dress or when supplemented to deficient diets. Lactation performance did not differ between AA-deficient or AA-adequate diets in response to RPL or RPLM supplementation.Conclusion: RPL or RPLM showed a positive linear relationship on the lactational performance of dairy cows whereas greater improvement effects were observed during early lactation. Supplementing RPL or RPLM is recommended on deficient-AA diet but not on adequate-AA diet.