Single-case experimental design (SCED) research plays an important role in establishing and confirming evidence-based practices. Due to multiple measures of a target behavior in such studies, missing information is common in their data. The expectation-maximization (EM) algorithm has been successfully applied to deal with missing data in between-subjects designs, but only in a handful of SCED studies. The present study extends the findings from Smith, Borckardt, and Nash (2012) and Velicer and Colby (2005b, Study 2) by systematically examining the performance of EM in a baseline-intervention (or AB) design under various missing rates, autocorrelations, intervention phase lengths, and magnitudes of effects, as well as two fitted models. Three indicators of an intervention effect (baseline slope, level shift, and slope change) were estimated. The estimates' relative bias, root-mean squared error, and relative bias of the estimated standard error were used to assess EM's performance. The findings revealed that autocorrelation impacted the estimates' qualities most profoundly. Autocorrelation interacted with missing rate in impacting the relative bias of the estimates, impacted the root-mean squared error nonlinearly, and interacted with the fitted model in impacting the relative bias of the estimated standard errors. A simpler model without autocorrelation can be used to estimate baseline slope and slope change in time-series data. EM is recommended as a principled method to handle missing data in SCED studies. Two decision trees are presented to assist researchers and practitioners in applying EM. Emerging research directions are identified for treating missing data in SCED studies.