A simple, precise, accurate and reproducible RP-HPLC method for simultaneous estimation of clarithromycin, pantoprazole and Metronidazole in bulk and pharmaceutical formulations. Separation of clarithromycin, pantoprazole and Metronidazole was successfully achieved on a YMC Pack Pro C18 (250 mm x 4.6mm x 5µ) in an isocratic mode utilizing sodium dihydrogen phosphate buffer and methanol (65:35 v/v) at a flow rate of 1.0 mL/min. The method was validated according to ICH guidelines for linearity, sensitivity, accuracy, precision, specificity and robustness. The response was found to be linear in the drug concentration range of 31-93.75 mg/mL for clarithromycin and 5-15 mg/mL for pantoprazole and 50-150 mg/mL for Metronidazole. The correlation coefficient was found to be 0.999 for both the drugs. The limit of detection (LOD) was 0.228, 0.0309 and 0.743 for clarithromycin, pantoprazole and Metronidazole respectively. The limit of quantification (LOQ) was 0.758, 0.1030 and 2.475 for clarithromycin, pantoprazole and Metronidazole respectively. The relative standard deviation (RSD) of six replicates is less than 2%. This HPLC method is applied successfully to the simultaneous quantitative analysis of clarithromycin, pantoprazole and Metronidazole in commercial tablets.