A rapid and sensitive isocractic RP-HPLC method has been developed for the purpose of analysis of losartan (LOS), hydrochlorothiazide (HCZ) and atorvastatin (ATR) drugs simultaneously in cardiovascular polypill. Analysis was performed on BDS Hypersil C18 (250 × 4.6mm id, 5-μm particle size) column with acetonitrile-0.2M phosphate buffer (pH 3) 50:50 (v/v) as mobile phase, a flow rate of 1.5 ml min-1 and column temperature 40 oC. UV detection was performed at 230 nm. The run time under these chromatographic conditions was less than 10 min. The method was linear in the range of 10-100 μg ml-1 for LOS, 10-90 μg ml-1 for HCZ and 10-150 μg ml-1 for ATR. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. The sensitivity of the method, as the limits of detection (LOD) and quantification (LOQ) for each active ingredient was also determined. The validated method was successfully applied for the quantification of losartan, hydrochlorothiazide and atorvastatin simultaneously in laboratory prepared pharmaceutical tablets and the average % amount ranges from 99.08 % to 99.60 % with relative standard deviation less than 1.5 % indicating satisfactory accuracy of the method.