The complex polymorphic system of the title compound, 5-ethyl,5-(1-methylbutyl)barbituric acid (Nbtl), is a key system for the general understanding of the molecular aggregation in barbiturates. The aim of this study was to establish a set of reliable data about the polymorphic behaviour of Nbtl and to resolve contradictions and inconsistencies between different previous reports. Four polymorphs of Nbtl, denoted Nbtl-I (m.p. 129.5 °C), Nbtl-II (126 °C), Nbtl-III° (114 °C) and Nbtl-IV (109 °C), were characterized by thermomicroscopy, differential scanning calorimetry (DSC), solution calorimetry, infrared and Raman spectroscopy, powder X-ray diffraction and single-crystal X-ray structure analysis. The DSC experiments indicated enantiotropic relationships for the two polymorph pairs I ↔ III° and I ↔ IV, and the corresponding endothermic transformations III°→I and IV → I occur at 106 °C and 90 °C, respectively. Nbtl-III° is the thermodynamically stable form at room temperature, as was confirmed by solvent-mediated transformation experiments, and the order of the thermodynamic stability at 20 °C is III° > IV > I > II. Nbtl-I and Nbtl-II are almost indistinguishable in their physical properties, which was found to be a consequence of their close structural similarity. These polymorphs represent similar packing modes of a common 2D supramolecular construct (SC), which itself is based on an N–H⋯OC bonded ribbon chain. The same 2D SC is also present in a co-crystal Nbtl·Pbtl, formed by Nbtl and phenobarbital (Pbtl; 5-ethyl,5-phenylbarbituric acid). Nbtl-III° displays a N–H⋯OC-bonded ribbon chain topology which is different from the chain type of Nbtl-I, -II and Nbtl·Pbtl. The molecules of Nbtl-IV are N–H⋯OC-bonded into corrugated sheets. Solvent screening experiments did not indicate the existence of any Nbtl solvates. This polymorphic system exemplifies the interplay of molecular conformation, the diversity of extended H-bonded structures and crystal packing.