A simple, fast, accurate, precise, method has been developed for the simultaneous estimation of Sulfadoxine and Trimethoprim in bulk and in pharmaceutical dosage forms by reversed-phase high performance liquid chromatography. The separation was carried out on C18 Phenomenex column, using mobile phase consisting of a mixture of acetonitrile: potassium dihydrogen orthophosphate buffer in the ratio 20: 80 and pH adjusted to 3.8 using orthophosphoric acid. The flow rate was adjusted to 1 ml/min. the UV detection was carried out at a wavelength of 248 nm. The retention time of Sulfadoxine and Trimethoprim was found to be 5.2 min and 2.4 min respectively. Linear response obtained for Sulfadoxine was in the concentration range 2-10 μg/ml (r2 = 0.999) and Trimethoprim in the range 1-5 μg/ml (r2 = 0.999). LOD for both the drugs were 0.0024 μg/ml and 0.0009 μg/ml respectively and LOQ for both the drugs were found to be 0.0072 μg/ml and 0.0028 μg/ml respectively. The method was validated according to ICH guidelines with respect to linearity, precision, accuracy, reproducibility, LOD, LOQ and robustness. Thus, proposed method can be successfully applicable to the pharmaceutical preparations containing the above mentioned drugs.