A simple sensitive, selective and accurate reversed-phase high performance liquid chromatographic method was developed and validated for the quantitative determination of lansoprazole, omeprazole and pantoprazole sodium sesquishydrate in the presence of their acid-induced degradation products. The three compounds were monitored at 280 nm using Nova-Pak C₁₈ column and a mobile phase consisting of 0.05 M potassium dihydrogen phosphate : methanol : acetonitrile (5 : 3 : 2 v/v/v). Linearity ranges were 2—20 μg ml⁻¹, 2—36 μg ml⁻¹ and 0.5—20 μg ml⁻¹ for lansoprazole, omeprazole and pantoprazole, respectively. The corresponding recoveries were 100.61±0.84%, 100.50±0.80% and 99.78±0.88%. The minimum detection limits were 0.55, 0.54 and 0.03 μg ml⁻¹ for lansoprazole, omeprazole and pantoprazole, respectively. The method could be successfully applied to the determination of pure, laboratory prepared mixtures and pharmaceutical dosage forms. The results obtained were compared with the reported methods for lansoprazole and pantoprazole or the official U.S.P method for omeprazole.