A simple, accurate and precise RP-HPLC method was developed and subsequently validated for simultaneous determination of Azithromycin and Ambroxol Hydrochloride in combined dosage form. The Proposed HPLC method utilizes C18 (250 mm × 4.6 mm × 5 µm) column with mobile phase comprising of KH2PO4 (pH 5.0 adjusted with 1 % Orthophosphoric acid: Methanol (60:40 % v/v) at a flow rate of 1.0 ml/min. Selection of wavelength for determination of Azithromycin (50 µg/ml) and Ambroxol Hydrochloride (15 µg/ml) show reasonably good response at 215 nm. Quantitation was achieved based on peak area with linear calibration curves at concentration ranges 25 - 75 µg/ml for Azithromycin and 7.5- 22.5 µg/ml for Ambroxol Hydrochloride with Correlation Coefficient of 0.999.The Retention times of Azithromycin and Ambroxol Hydrochloride were found to be 6.73 min and 4.17 min respectively. The limit of detection (LOD) was 0.36 and 0.18 for Azithromycin and Ambroxol Hydrochloride respectively. The limit of quantification (LOQ) was 1.09 and 0.56 for Azithromycin and Ambroxol Hydrochloride respectively. The accuracy was found within the limit. The precision (inter - day, intra - day and repeatability) was found within the limit. The method was validated as per ICH guideline. The method can be successfully employed for simultaneous estimation of Azithromycin and Ambroxol Hydrochloride in combined dosage form.