<p>A simple and reliable high-performance thin-layer chromatography (HPTLC) assay was developed and validated in accordance with the International Council for Harmonisation (ICH) guidelines for the quantification of progesterone in pharmaceutical formulations. The assay was carried out on silica gel 60 F₂₅₄ HPTLC plates, hexane–ethyl acetate (3:1, <i>V/V</i>) was chosen as mobile phase, and the analysis performed at 255 nm. The method was found to meet ICH requirements for specificity, linearity, sensitivity, precision, accuracy, repeatability, and robustness. Progesterone presented as a sharp band at <i>R</i>_F 0.13, and there was good linearity between the 25 and 200 ng/band concentration range (<i>r</i>² = 0.999). Limit of detection and limit of quantification were calculated to be 7.78 ng and 23.57 ng, respectively; the mean drug recovery was found to be between 100.58% and 104.32%. The developed and validated assay was applied to the analysis of commercial pessaries containing 400 mg progesterone and to a progesterone cream compounded to a strength of 180 mg/g cream. The formulations were found to have drug contents, respectively, of 99.76% (± 1.35%) and 100.92% (± 2.72%) of labeled claim. The method is therefore suitable for the quantification and quality control of progesterone in pharmaceutical formulations.</p>