A high performance liquid chromatographic method with amperometric detection has been developed for the determination of the diuretic xipamide using a μ-Bondapak C18column. The mobile phase consisted of a mixture water:acetonitrile 50:50, 5 mM in KH2PO4/K2HPO4, pH 4.3. The compound is monitored at +1325 mV with an amperometric detector equipped with a glassy carbon working electrode. A liquid-liquid or solid-liquid extraction prior to chromatographic analysis was done to avoid the interferences found in urine matrix. Percentages of recovery were (99.3±4.7) and (99.4±4.2) for liquid-liquid and solid-liquid extraction, respectively. The method developed has a linear concentration range from 0.05 to 0.50 μg/mL, with a reproducibility in terms of relative standard derivation (RSD) for a concentration level of 1 μg/mL of 4% and a quantitation limit of 0.50 ng/mL. The method was applied to the determination of xipamide in tablets and urine obtained from hypertensive patients after the ingestion of Demiax (xipamide 20 mg).