A new second-order calibration procedure, the coupled vectors resolution (COVER) method, has been developed. The objective of the method is to seek a couple of vectors that minimize a least-squares criterion. With the knowledge indispensable for quantitation, the method yields direct solutions to various cases of second-order calibration. Moreover, it allows a statistically plausible way to make use of multisample information. In the case of multiple calibration samples, the method uses the calibration samples to resolve the profiles of the analytes in each order, and then calculates the concentrations of the analytes. This offers the advantage that unknown mixtures newly collected can be predicted in a direct manner. In the case of one calibration sample, the method provides an effective way to utilize the information of spectral profiles of the analytes. Results of simulated experiments and a real analytical example show that the proposed method produces acceptable performance in profile resolution and concentration estimation.