Buflomedil HCl, was reduced at the mercury electrode in buffered solutions of various pH values (2-11) via a single 2-electron irreversible step corresponding to reduction of its C=O double bond. Buflomedil HCl has interfacial adsorptive behavior onto the mercury electrode surface and a monolayer surface coverage of 2.37 × 10-10 mol cm-2 was estimated. Each adsorbed buflomedil HCl molecule was found to occupy an area of 0.69 nm2 onto the HMDE surface. Differential-pulse (DP), liner-sweep (LS) and square-wave (SW) adsorptive cathodic stripping voltammetry (AdCSV) methods were described for its determination in the bulk form. The sensitivity of the described electro-analytical methods increases in the direction: DP-AdCSV < LS-AdCSV < SW-AdCSV since their achieved limits of detection were: 2.4 × 10-8, 1.5 × 10-8 and 1.2 × 10-9 M bulk buflomedil HCl, respectively. Besides, a simple high-performance liquid chromatographic method was also developed for determination of bulk buflomedil HCl with a detection limit of 3.0 × 10-8 M. The described voltammetric and chromatographic methods were successfully applied for determination of buflomedil HCl in its formulations. Besides these methods were applied for determination of buflomedil HCl in spiked human serum (limit of detection varying from 1.5 × 10-9 to 4.5 × 10-8 M buflomedil HCl) without the necessity for pretreatment and/or time-consuming extraction steps prior to the analysis. No significant interferences from excipients or from endogenous human serum substances were obtained. The described SW-AdCS voltammetry method is much more sensitive than the described chromatographic one. However the described chromatographic method is substantially simpler, faster and more sensitive than the previously reported HPLC methods.