Herein we report the results of a comparative study on the performance of Monolithic RP-18e and Platinum C(18) 3 mum columns for isocratic separation of acidic and basic test compounds. The inter- and intraday precision of different practical parameters including number of theoretical plates (N), capacity factor (K'), tailing factor (T(0.05)), and resolution (R(s)) were determined for both columns. Two different production batches were used for each column and batch to batch reproducibility of both columns was evaluated. The column backpressure drop over flow rate range 0.5-2 mL/min at the monolithic columns was two- to three-times lower than that on the platinum column without loss of the column efficiency. The plate heights were used to estimate the columns efficiency using Van Deemter plots. Both types of columns were able to separate the tested compounds well with sufficient resolution and peak symmetry but they differ in the analysis time and column backpressure, significantly. Monolithic column was more convenient as it enables the analytical run under low backpressure at shorter time with sufficient separation efficiency.