Researchers and practitioners often use single-case designs (SCDs), or n-of-1 trials, to develop and validate novel treatments. Standards and guidelines have been published to provide guidance as to how to implement SCDs, but many of their recommendations are not derived from the research literature. For example, one of these recommendations suggests that researchers and practitioners should wait for baseline stability prior to introducing an independent variable. However, this recommendation is not strongly supported by empirical evidence. To address this issue, we used Monte Carlo simulations to generate graphs with fixed, response-guided, and random baseline lengths while manipulating trend and variability. Then, our analyses compared the type I error rate and power produced by two methods of analysis: the conservative dual-criteria method (a structured visual aid) and a support vector classifier (a model derived from machine learning). The conservative dual-criteria method produced fewer errors when using response-guided decision-making (i.e., waiting for stability) and random baseline lengths. In contrast, waiting for stability did not reduce decision-making errors with the support vector classifier. Our findings question the necessity of waiting for baseline stability when using SCDs with machine learning, but the study must be replicated with other designs and graph parameters that change over time to support our results.