A new simple, sensitive, rapid, precise, and accurate reverse phase high performance liquid chromatographic method had developed for the simultaneous estimation of guaifenesin and pseudoephedrine HCl in ER tablet dosage form. The components separated by using Zorbax SB Phenyl (150 × 4.6 mm i.d × 5 μm) column with UV detection at 210 nm. The mobile phase solvent A and B in the ratio of 950:50 v/v, flow rate was found to be 2 ml/min and run time detected in 15 min. Guaifenesin and pseudoephedrine HCl were eluted with retention time of 10.64 min and 2.635 min. The method validated for linearity, accuracy, precision, robustness, and ruggedness as per ICH guidelines and results found within the acceptable limits. The linearity for guaifenesin and pseudoephedrine HCl had found in the range of 96-721 μg/ml and 10-72 μg/ml. The validated method had applied for the routine analysis of these compounds in ER tablet dosage form.