Abstract The effect of molecular characteristics of EO–PO triblock copolymers viz. Pluronic® P103 (EO17PO60PEO17), P123 (EO19PO69EO19), and F127 (EO100PO65EO100) on micellar behavior and solubilization of a diuretic drug, hydrochlorothiazide (HCT) was investigated. The critical micellization temperatures (CMTs) and size for empty as well as drug loaded micelles are reported. The CMTs and micelle size depended on the hydrophobicity and molecular weight of the copolymer; a decrease in CMT and increase in size was observed on solubilization. The solubilization of the drug hydrochlorothiazide (HCT) in the block copolymer nanoaggregates at different temperatures (28, 37, 45°C), pH (3.7, 5.0, 6.7) and in the presence of added salt (NaCl) was monitored by using UV–vis spectroscopy and solubility data were used to calculate the solubilization characteristics; micelle–water partition coefficient (P) and thermodynamic parameters of solubilization viz. Gibbs free energy (ΔGs°), enthalpy (ΔHs°) and entropy (ΔSs°). The solubility of the drug in copolymer increases with the trend: P103>P123>F127. The solubilized drug decreased the cloud point (CP) of copolymers. Results show that the drug solubility increases in the presence of salt but significantly enhances with the increase in the temperature and at a lower pH in which drug remains in the non-ionized form.