Direct reductive amination (DRA) is one of the most efficient methods for amine synthesis. Herein we report a practical homogeneous DRA procedure utilizing iridium catalysis. Applying simple, readily available and inexpensive PPh3 and alike ligands at as low as 0.003 mol%, aldehydes and ketones reductively coupled with primary and secondary amines to efficiently form structurally and functionally diverse amine products, including a set of drugs and their late-stage manipulation. The reaction conditions were exceptionally mild and additive-free, and they tolerated oxygen, moisture, polar protic groups and multiple other functional groups. For targeted products, this methodology is versatile and could offer multiple synthetic routes in regard to the selection of starting materials. The 10 gram-scale synthesis further demonstrated the potential and promise of this procedure in practical amine synthesis.