Per- and polyfluoroalkyl substances (PFASs), or Per- and polyfluorinated compounds (PFCs), represent a group of anthropogenic chemicals that have been produced and widely used in industrial applications and consumer products since the 1950s. The unique physical and chemical characteristics of these compounds (highly stable and resistant to degradation), along with their ubiquitous use, have led to the accumulation of PFAS in the environment, with growing concern of human exposure to these chemicals. The most widely used analytical method for PFAS monitoring is LC/MS/MS owing to its high sensitivity, selectivity and robustness. Recently, with the advancement and availability of highly sensitive mass spectrometers, a trend towards developing a high throughput analytical method for monitoring PFASs by direct injection without SPE has been appreciated. The direct injection approach can achieve higher levels of sample throughput, and reduce potential analyte loss and contamination caused by SPE sample preparation, as demonstrated by this study using PerkinElmer’s QSight® 420 mass spectrometer, coupled with UHPLC for the determination of trace amount of PFOA and PFOS in drinking and surface water samples.