A simple, precise bioanalytical UPLC Tandem Mass Spectroscopy gradient elution method was developed and validated for simultaneous estimation of Olmesartan Medoximil (OLM) and Metoprolol Succinate (MET) in human plasma. The quantitation carried out using Shimadzu Shimpack-C18 GIST AQ (50 mm X 2.1 mm, 1.9 µm) column and the mobile phase A comprises of 0.1% formic acid and mobile phase B as acetonitrile used for gradient elution. Analysis completed within run time of 4 min at the mobile phase flow rate of 0.3mL/min. The retention time of metoprolol succinate and olmesartan medoximil were 1.029 min and 2.514min, respectively. Analytes were extracted using acetonitrile as extracting solvent. The method validated in terms of linearity, accuracy, precision, lower limit of quantitation, method sensitivity and various solution stability parameters. Linearity of olmesartan medoximil and metoprolol succinate was in the range of 5-1500ng/mL. All the method validation parameters were determined as per ICH, EMA and FDA guidelines and falls under the stated acceptance criteria. The presented work provides a validated bioanalytical method for simultaneous determination of olmesartan medoximil and metoprolol succinate in human plasma. The method is accurate, simple, precise, fast and suitable for its application for bioequivalence and pharmacokinetic studies. © RJPT All right reserved.