Fast, simple, accurate, and reproducible reverse phase‐high‐performance liquid chromatography method with direct ultraviolet measurement of memantine hydrochloride in tablets was developed, without any chemical derivatization pretreatment. Three main problems appear during chromatographic analysis of memantine: detection, achieving appropriate column retention, and limited choice of mobile phase components, as a result of memantine molecular structure. Among more than 35 tested columns, the best retention and peak symmetry yielded two C8 and three C18 columns with different characteristics, at a temperature of 30°C, mobile phase composed of 1%, v/v, acetonitrile and 99%, v/v, of 0.05–0.1% phosphoric acid or 2.5–5 mmol phosphate buffer, at flow rate of 1 mL/min and injection volume of 5 µL. The retention time of memantine was between 2.6 and 4 min. Both mobile phase concepts showed perfect linearity, precision, and accuracy. This is the first successful and reproducible direct reverse phase‐high‐performance liquid chromatography–ultraviolet quantification method for memantine.