Currently, LC-MS/MS and GC-MS are the most common techniques used for acrylamide analysis in foods. However, these techniques require extensive sample preparation, highly specialized machinery, and are time consuming. Our objective was to evaluate the feasibility of using attenuated total reflectance (ATR) mid-infrared microspectroscopy (IRMS) as a rapid method for detection and quantification of acrylamide in potato chips. The acrylamide content of 58 commercially available potato chips (110-1876 mu g kg(-1)) was determined by LC-MS/MS. Spectra for aqueous extracts of potato chips with and without solid phase extraction (SPE) clean-up were collected using ATR-IRMS. Partial Least Squares Regression (PLSR) was applied to generate calibration models to predict acrylamide levels. Samples were grouped into three categories: regular potato chips (n = 46), potato chips with seasonings (n = 12) and combination of regular and seasoned potato chips (n = 58). Overall, a good linear correlation was found between the predicted acrylamide levels of independent sample sets and actual measured acrylamide concentrations by LC-MS/MS (rPred was between 0.91 and 0.92). Standard error of prediction (SEP) for the models ranged between 22.1 and 28.9 mu g L-1. Models developed without SPE cleaning provided similar or better results than those with SPE treatment, which makes IRMS technology even more promising for acrylamide analysis since the SPE step can be avoided. Our results indicate that IRMS can be used as a simple, rapid and high-throughput screening tool for acrylamide detection and quantification in potato chips and help addressing risk management, assessing safety and brand equity.