A nontarget screening method was developed based on D-optimal designs for ultra-high performance supercritical fluid chromatography with positive and negative electrospray ionisation mode MS. A mixture of organic contaminants such as pesticides, steroids, surfactants, phenolic and fatty acids, and polycyclic aromatic hydrocarbon derivatives, was used for the optimisation. An aprotic mixture of dichloromethane and acetone [3:1] performed overall best as the injection solvent. The highest peak capacities (n) were accomplished at the shallowest gradient (1%Bmin -1 ), ammonium formate (n = 378 in negative ionisation mode) or ammonium acetate (n = 327 in positive ionisation mode) in methanol as the modifier. Capillary voltage, make-up solvent flow rate, water and additive concentration were the most significant factors for improving peak intensity: higher peak intensities were obtained at lower additive concentrations (5mM ammonium formate), and with 5% water in positive ionisation mode. Conversely, water had detrimental effects in negative ionisation mode. The optimised method was used to quantify organic contaminants in 17 freshwater sediment samples from Copenhagen, Denmark. Out of 50 monitored contaminants, 35 were detected in at least one sample. Further, the method has a potential for target and nontarget screening analysis of organic contaminants in solid matrices. This article is protected by copyright. All rights reserved.