Soybean meal (SBM) is an excellent protein source for pigs because of its well-balanced amino acid profile and its competitive cost compared to other protein sources. In addition, SBM contains a significant amount of health-promoting compounds, such as isoflavones, saponins, and phenolic antioxidants that can modulate immune responses and improve growth performance of pigs exposed to viral disease challenges. With the availability of distillers’ dried grains with solubles (DDGS) and cost-effective crystalline amino acids, the levels of dietary SBM have been driven to very low levels, especially in late finishing diets, largely eliminating the growth- and potential health-promoting benefits that SBM may provide. We showed in growing pigs (38.5 to 73.2 kg, 512 pigs) that pigs fed DDGS (25%) had a 1.12 kg lower body weight at the end of the study, whereas replacing SBM with 0.60% of lysine HCl (plus other crystalline amino acids) reduced final body weight by 2.59 kg. Supplementation of crystalline amino acids decreased final body weight, growth rate and feed intake linearly when DDGS were not included in the diet, whereas the response was quadratic in DDGS diets. Feed:gain was 3.2% higher for pigs fed diets with DDGS compared to control- fed pigs, consuming 0.08 kg more feed per kg of gain. Feeding diets with supplemental crystalline amino acids (0.60% supplemental lysine HCl) resulted in a 4.2% higher feed:gain or 0.10 kg more feed-per-kg of gain. In finishing pigs (83.1 to 124.7 kg; 480 pigs), inclusion of DDGS reduced average daily gain and tended to decrease daily feed intake without affecting feed efficiency. Supplemental crystalline amino acids linearly decreased average daily gain and worsened feed efficiency. Pigs fed DDGS to displace SBM were 1.22 kg lighter at marketing with a feed efficiency that was similar between the two groups. Inclusion of 0.60% lysine HCl while balancing other essential amino acids decreased final market weight by 2.74 kg and increased feed:gain by 5.0% which was equivalent to 0.16 kg of extra feed-per-kg of gain. In both studies, replacement of SBM was carefully balanced through formulation of diets that met or exceeded requirements for standardized ileal digestible lysine, methionine plus cystine, threonine, tryptophan, valine and isoleucine and were equal in net energy content.