The aim of this study was to develop a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based method for the multiresidue analysis of 21 plastic additives in river water. Analysed compounds included phthalates, benzophenone, bisphenol A and long- and short-chain alkylphenols (APs), which are of relevance because most of them are high production volume chemicals largely used in the plastic industry. These compounds can reach river waters due to direct discharge from wastewater treatment plants and leaching from plastic materials and microplastics present in rivers. In a first step, ionisation and acquisition parameters were optimised to obtain high sensitivity and structural information. Then, different solid-phase extraction cartridges and elution conditions were tested using Milli-Q and river water. With the optimised conditions, quality control parameters (recoveries, limits of detection, intra- and inter-day variability and blank contribution) proved that the method was accurate and selective for the trace monitoring of these compounds in river water. For nonylphenol, octylphenol and bis(2-ethylhexyl)phthalate, included in the Water Framework Directive, limits of detection were below environmental quality standard concentrations considering blank contributions. All other compounds were efficiently detected at trace levels, and focus was given too- andp-substituted and di- and tri-substituted APs, which are first reported in the present study. A pilot survey was finally carried out to determine the occurrence of plastic additives in river waters surrounding the city of Barcelona.