This meta-analysis of the experimental literature of distance education (DE) compares different types of interaction treatments (ITs) with other DE instructional treatments. ITs are the instructional and/or media conditions designed into DE courses, which are intended to facilitate student–student (SS), student–teacher (ST), or student–content (SC) interactions. Seventy-four DE versus DE studies that contained at least one IT are included in the meta-analysis, which yield 74 achievement effects. The effect size valences are structured so that the IT or the stronger IT (i.e., in the case of two ITs) serve as the experimental condition and the other treatment, the control condition. Effects are categorized as SS, ST, or SC. After adjustment for methodological quality, the overall weighted average effect size for achievement is 0.38 and is heterogeneous. Overall, the results support the importance of the three types of ITs and strength of ITs is found to be associated with increasing achievement outcomes. A strong association is found between strength and achievement for asynchronous DE courses compared to courses containing mediated synchronous or face-to-face interaction. The results are interpreted in terms of increased cognitive engagement that is presumed to be promoted by strengthening ITs in DE courses.