Many experiments aim to investigate the time-course of cognitive processes while measuring a single response per trial. A common first step in the analysis of such data is to divide them into a limited number of bins. As we demonstrate here, the way one chooses these bins can considerably influence the resulting time-course. As a solution to this problem, we here present the smoothing method for analysis of response time-course (SMART)—a complete package for reconstructing the time-course from one-sample-per-trial data and performing statistical analysis. After smoothing the data, the SMART weights the data based on the effective number of data points per participant. A cluster-based permutation test then determines at which moments the responses differ from a baseline or between two conditions. We show here that, in contrast to contemporary binning methods, the chosen temporal resolution has a negligible effect on the SMART reconstructed time-course. To facilitate its use, the SMART method, accompanied by a tutorial, is available as an open-source package.