The aim of the present work was to develop and validate a simple, efficient and economical method for the analysis of Guaifenesin and Phenylephrine hydrochloride in bulk drug and pharmaceutical dosage forms by reverse phase high pressure liquid chromatography. A Zorbax reverse phase C18 column (150 x 3.0mm, 3.5μm) with mobile phase containing 5mM ammonium acetate: acetonitrile (80:20% v/v) was used at isocratic mode and eluents were monitored at 222nm. The retention time of Phenylephrine hydrochloride was 1.62 min and Guaifenesin was 2.28 min and showed a good linearity in the concentration range of 1-5μg/mL for Phenylephrine hydrochloride and 15- 75μg/mL for Guaifenesin with a correlation coefficient >0.999. The validation characteristics included specificity, linearity, and limit of detection, limit of quantification, precision, assay, accuracy, robustness and stability. Validation acceptance criteria were met in all cases. The percent recoveries ranged in between 98-102 (RSD < 2). The method was successfully used for the simultaneous analysis of Phenylephrine hydrochloride and Guaifenesin in bulk drug and pharmaceutical dosage forms.