Abstract Widely used as flame retardants, organophosphate esters (OPEs) are now broadly present in the indoor and outdoor environments. Currently available liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods share some drawbacks with gas chromatography (GC) methods, including time consuming, limited target OPEs, incomplete separation capability for some OPEs and low throughput. In this study, a fast and high throughput LC–MS/MS method was developed. For the first time, all the twelve OPEs that have been studied in literature, ranging from the very polar and volatile trimethyl phosphate to the very hydrophobic and non-volatile tris(2-ethylhexyl) phosphate, were separated within 11 min. Different from previous studies, we found that the blank contamination was mainly from organic mobile phase rather than the enrichment process, and it can be efficiently eliminated by using acetonitrile rather than methanol as the organic phase of the mobile phase. The signal to noise ratio (S/N) was significantly improved by using 0.1% formic acid as an organic modifier. The method exhibited high throughput and sensitivity and can baseline separate 11 of the 12 OPEs studied within 11 min with LOQs ranging from 2 to 6 ng/L. The relative standard deviations were in the range of 2–10%. For both reagent water and river water, the spiked recoveries of OPEs ranged from 70 to 110%, except for the very polar and volatile trimethyl phosphate that has recovery below 10%. The developed procedure was successfully applied to study the OPE contamination of the Songhua River, and it was found that all the target OPEs were detected with total concentrations of around 1 μg/L in the river waters.