Corrosion inhibitors (CIs) are extensively employed in the oil and gas industry, yet their analysis remains a challenge. To develop a suitable liquid chromatography method for a wide array of CIs, a column screening was conducted. Nine different chromatographic conditions were tested across eight RPLC and mixed‐mode columns (Accucore C18, CORTECS Shield RP18, Acquity HSS T3, Acquity Premier HSS T3, Accucore 150‐C4, Accucore PFP, Synergi Polar RP, and Acclaim WCX‐1). Seven model mixtures representative of CIs, which included quaternary ammoniums, imidazolines, and phosphoric esters, were considered to probe the columns. Each column exhibited unique analytical performances, peak shape, and separation profiles. To find a compromise to analyze all the mixtures with one method, Derringer desirability functions were used. Shielding of residual silanols proved to be a critical factor. The trifunctional grafting of the Acquity HSS T3 columns appeared to be a promising strategy to minimize residual silanol effects. However, it was the Premier technology, which protects the column's inner walls and frits against parasitic adsorption, which delivered the best overall results. Based on the desirability study, the Acquity Premier HSS T3 column was selected and the gradient was optimized, which enabled the separation of the molecules present in the model mixtures.