A RP- HPLC method is described for the determination of Nelfinavir Mesylate in tablet dosage form. Chromatography was carried on an ODS column using a mixture of methanol and water (80:20 v/v) instead of Acetonitrile and phosphate buffer pH 6 (90:10 v/v) as the mobile phase at a flow rate of 1.2 mL/min with detection at 230 nm. The retention time of the drug was 6.68 min. The detector response was linear in the concentration of 1-20 mcg/mL the limit of detection and limit of quantification was 1.0 and 10.0 mcg/ mL respectively. The percentage assay of Nelfinavir Mesylate was 99.77 %. The method was validated by determining its sensitivity, accuracy and precision. The proposed method is simple, fast, accurate and precise and hence can be applied for routine quality control of Nelfinavir Mesylate in bulk and tablet dosage form.