Abstract This study evaluated the effect of replacing soybean meal (SBM) with DDGS and crystalline amino acids on growth and carcass lean. Pigs (n = 512; 38.51±0.13 kg BW) were blocked by BW and sex and placed in 64 pens (4 gilts and barrows per pen). Treatments were arranged as a 2×4 factorial with DDGS included at 0 or 25% and L-lysine-HCl (LYS) added at 0, 0.2, 0.4, and 0.6%. Dietary SBM inclusion declined as LYS increased from 32.06 to 13.14% (Phase 1) and 28.25 to 9.40% (Phase 2) for control diets. It declined from 27.85 to 8.89% (Phase 1) and 24.05 to 5.10% (Phase 2) for DDGS diets. Diets contained 1.00 (Phase 1, 21 days) and 0.90% (Phase 2, 18 days) SID lysine and were balanced for ideal protein and net energy. During Phase 1, DDGS decreased ADG (P = 0.06; 786 vs. 821 g/d). Increasing LYS increased (quadratic, P ≤ 0.05) ADG and ADFI with the greatest response at 0.4% LYS. G:F decreased (linear, P = 0.035) with increasing LYS. During Phase 2, increasing LYS in control, but not DDGS diets, decreased (linear, P < 0.005) ADG and ADFI. G:F declined (P = 0.054) with DDGS inclusion (370 vs. 383 g/kg). Overall, ADG decreased (linear, P = 0.005) as LYS increased in control (959, 929, 908, 860 g/d), but not DDGS diets (863, 908, 931, 832 g/d). ADFI decreased (linear, P = 0.014) with increasing LYS in control (2270, 2198, 2186, 2130 g/d), but increased (quadratic, P = 0.039) in DDGS diets (2112, 2207, 2324, 2103 g/d). DDGS reduced (P≤0.03) ADG (883 vs. 914 g/d), G:F (405 vs. 417 g/kg) and LEA (34.5 vs. 35.3 cm2), while increasing LYS decreased (linear, P < 0.005) G:F (417, 419, 409, 401 g/kg) and LEA (35.34, 35.17, 35.46, 33.64 cm2). Displacement of SBM with DDGS reduced growth and LYS addition negatively affected growth and G:F for diets with SBM, but not DDGS.