Problem-based learning (PBL) is an instructional strategy that is poised for widespread application in the current, growing, on-line digital learning environment. While enjoying a track record as a defensible strategy in face-to-face learning settings, the research evidence is not clear regarding PBL in on-line environments. A review of the literature revealed that there are few research studies comparing on-line PBL (oPBL) to face-to-face PBL, and, in these, findings have been mixed. This study is a combined meta-analytic and qualitative review of the existing research literature comparing oPBL to face-to-face PBL. The study's aim is to: (1) Detect the presence and magnitude of the effectiveness of oPBL; and (2) Uncover and identify the factors that contribute or explain the effectiveness of oPBL. This review used a mixed methods strategy, combining a meta-analysis with a qualitative analysis of the studies that met inclusion criteria. An overall effect size was found to be slightly in favour of oPBL in terms of student performance outcomes. The qualitative analysis revealed relationships between established concepts of learning. The observations in this systematic review help reduce uncertainty about the robustness of PBL as in instructional strategy delivered in the online environment. (Contains 3 tables and 6 figures.)