A rapid and simple high-performance liquid chromatographic (HPLC) method for the analysis of docusate sodium in soft gelatin capsules was developed with progesterone as the internal standard. The method requires a reversed-phase column and a paired-ion technique to separate docusate sodium from other components. A C22 column was used with a mobile phase of acetonitrile:water (70:30) containing 0.005 M tetrabutylammonium phosphate. The flow rate was 1.8 mL/min, and the effluent was monitored at 214 nm. Docusate sodium and progesterone had retention times of 4.5 and 6.8 min, respectively. The proposed HPLC method is linear, accurate, and precise. A mean assay value of 99.6% was obtained by the proposed method when five samples, each containing a composite of 10 capsules, were analyzed. The results obtained by the proposed HPLC, tetra-n-butylammonium iodide titration, and USP XXII HPLC methods are compared.