A high-performance thin-layer chromatographic (HPTLC) method was performed for simultaneous quantification of four angiotensin II receptor antagonists, namely, losartan, irbesartan, valsartan, and olmesartan. The method based on HPTLC separation of the four drugs using reflectance-absorbance mode at 255 nm. Separation was carried out on pre-coated silica gel HPTLC plates, using chloroform-glacial acetic acid (7.5:2.5, v/v) as mobile phase. The four drugs have been satisfactorily resolved with R_F values of 0.23 ± 0.01, 0.36 ± 0.01, 0.45 ± 0.01, and 0.78 ± 0.01 for olmesartan, losartan, irbesartan, and valsartan, respectively. The method was validated according to the International Conference on Harmoni zation (ICH) guidelines. The linear regression analysis data for the calibration plots of all studied drugs produced a good linear relationship with correlation coefficients ranging from 0.9988 to 0.9996 and coefficients of determination ranging from 0.9976 to 0.9990 over the concentration range of 90–750 ng per band. The limits of detection and quantification for all studied drugs ranged from 14.85 to 30.42 and from 45.00 to 92.18 ng per band, respectively. The developed method was applied successfully for the determination of the studied drugs in pharmaceutical formulations and spiked human plasma with good precision and accuracy.