The accurate prediction of rate constants for chemical reactions in solution, using computational methods, is a challenging task. In this work, a computational protocol designed to be a reliable tool in the study of radical-molecule reactions in solution is presented. It is referred to as quantum mechanics-based test for overall free radical scavenging activity (QM-ORSA) because it is mainly intended to provide a universal and quantitative way of evaluating the free radical scavenging activity of chemical compounds. That is, its primary antioxidant activity. However, it can also be successfully applied to obtain accurate kinetic data for other chemical reactions in solution. The QM-ORSA protocol has been validated by comparison with experimental results, and its uncertainties have been proven to be no larger than those arising from experiments. Further applications of QM-ORSA are expected to contribute increasing the kinetic data for free radical-molecule reactions relevant to oxidative stress, which is currently rather scarce. © 2013 Wiley Periodicals, Inc.