Tris(hydroxymethyl) aminomethane (tris) salt of API ramipril was synthesized, and characterized by FTIR, TG-DSC and ab initio X-ray powder structure analysis. The compound, ramipril-tris (II), crystallizes in the monoclinic space group P2(1) with a=24.3341(15), b=6.4645(5), c=9.5357(7) Å, β=96.917(3)° and V=1489.1(3) Å(3). The crystal structure has been determined from laboratory X-ray powder diffraction data using direct space global optimization strategy (simulated annealing) followed by the Rietveld refinement. A network of intermolecular OH…O, CH…N and CH…O hydrogen bonds between the ramipril-ramipril, tris-tris and ramipril-tris components in the compound generates a two-dimensional molecular assembly in (110) plane. A comparative study of solid-state stabilities of ramipril-tris (II) with that of ramipril (I) and ramipril-erbumine (III) indicates that ramipril-tris (II) is the most stable one among the three, and the conversion to impurity D after 72 h at 80 °C is only 1.5%. The solution phase analysis at different pH values also reveals a greater stability of ramipril-tris (II) over ramipril (I).