High-performance liquid chromatographic (HPLC) method has been developed and validated for the simultaneous determination of diltiazem and statins in raw materials, their pharmaceutical formulations and human serum. In HPLC, diltiazem and statins are chromatographed using acetonitrile–water (85 : 15 v/v, pH 2.6 ± 0.02) as the mobile phase at a flow rate of 1.0 mL min⁻¹ at ambient temperature. The separation is carried out on a Hiber®, 250-4.6 RP-18 column, equipped with a UV/visible detector at 230 nm. All the statins eluted at a different retention time and each showed good resolution from diltiazem. The method has been successfully applied to pharmaceutical formulations because no chromatographic interferences from the tablet excipients are found. The linearity is found to be in the range 0.625–20 μg mL⁻¹. The suitability of the method for the quantitative determination of the drugs is proven by validation in accordance with the requirements laid down by the International Conference on Harmonization (ICH) guidelines. The validation results, together with statistical treatment of the data, demonstrated the reliability of this method.