This disclosure provides a natriuretic peptide derivative of Formula (I), and to compositions including a natriuretic peptide derivative of Formula (I), [in-line-formulae](fatty acyl)z-(B)x-(G)y-NP?? (I), [/in-line-formulae]wherein : z is 1, x is an integer from 2 to 4 and y is 3; or z is 0, x is an integer from 0 to 4 and y is an integer from 1 to 3; fatty acyl comprises from 12 to 24 (e.g., 12 to 18) carbons atoms; B is lysine or arginine; G is glycine; NP is a natriuretic peptide; if present, (fatty acyl)z- is covalently linked to the N-terminus of (B)x; (fatty acyl)z-(B)x- is covalently linked to the N-terminus of (G)y; and (fatty acyl)z-(B)x-(G)y- is covalently linked to the N-terminus of NP. The natriuretic peptide derivative according to the disclosure, and compositions thereof, are useful in the treatment of diseases such as hypertension, vascular congestion, and heart disease.