Single-case experimental methods are used across a range of educational and psychological research. Single-case data are analyzed with a variety of methods, but no statistic has demonstrated clear superiority over other methods. The time-series nature of single-case designs requires special consideration for baseline trend and autocorrelation when estimating intervention effect size. However, standard correction methods are limited because they assume precise statistical estimation of trend and autocorrelation. Unlike standard correction methods, Monte Carlo simulation methods can address the poor precision of single-case effect size indices. This paper presents the rationale for a new simulation method, Interrupted Time-Series Simulation (ITSSIM). A small field test was also conducted, and ITSSIM performed similarly to sophisticated multilevel methods for single-case research. ITSSIM is accessible as a free software application that requires no prior knowledge of statistical computing or syntax. ITSSIM may be used to estimate the effect size of a single interrupted time-series (AB design), and multiple ITSSIM effect size estimates may be combined via meta-analysis.