A simple and reliable isocratic reversed-phase high-perfomance liquid chromatographic (RP-HPLC) method has been developed and validated for the simultaneous estimation of Enalapril Maleate(ENL), hydrochlorothiazide(HCT), aspirin(ASP) and atorvastatin(ATR) in bulk and its simulated dosage form. All the drugs were separated on a 250mm×4.6mm C18 column packed with 5 μm particles. The mobile phase, optimized through an experimental design, was a 50:25:25 (v/v/v) mixture of acetontrile, methanol and triethylammonium phosphate buffer (pH 2.5), pumped at a flow rate of 0.6 ml/min. UV detection was performed at 225 nm. The retention time of ENL, HCT, ASP and ATR was found to be 3.667 min, 4.725 min, 5.508 min and 8.282 min respectively. The method was validated in the sample concentration ranges of 25-500 μg/ml for ENL, 12.5-250 μg/ml for HCT, 12.5-250 μg/ml for ASP and 50-1000 μg/ml for ATR, where it demonstrated good linearity with correlation coefficient values of 0.999 (n = 3) for all the drugs in the study. The method demonstrated to be robust, resisting to small deliberate changes in pH and flow rate of the mobile phase. The LOD values were 1.474μg/ml, 0.737μg/ml, 0.545μg/ml and 1.641μg/ml, while the LOQ values were 4.466μg/ml, 2.233μg/ml, 1.653μg/ml and 4.972μg/ml for ENL, HCT, ENL and ATR respectively. The recoveries for all four compounds were above 98%. The applicability of the method was demonstrated by determining the drug content in simulated pharmaceutical formulation, where it exhibited good recovery. Hence the method can easily applicable for routine quality control laboratories.