Objectives: To examine the best practice evidence of the effectiveness of the flipped classroom (FC) as a burgeoning teaching model on the development of self-directed learning in nursing education. Data sources: The relevant randomized controlled trial (RCT) and non-RCT comparative studies were searched from multiple electronic databases including PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), Wanfang Data, China National Knowledge Infrastructure (CNKI), and Chinese Science and Technology Periodical Database (VIP) from inception to June 2017.Review methods: The data were independently assessed and extracted for eligibility by two reviewers. The quality of included studies was assessed by another two reviewers using a standardized form and evaluated by using the Cochrane Collaboration's risk of bias tool. The self-directed learning scores (continuous outcomes) were analyzed by using the 95% confidence intervals (CIs) with the standard deviation average (SMD) or weighted mean difference (WMD). The heterogeneity was assessed using Cochran's I 2 statistic. Results: A total of 12 studies, which encompassed 1440 nursing students (intervention group = 685, control group = 755), were eligible for inclusion in this review. Of 12 included studies, the quality level of one included study was A and of the others was B. The pooled effect size showed that compared with traditional teaching models, the FC could improve nursing students' selfdirected learning skill, as measured by the Self-Directed Learning Readiness Scale (SDLRS), Self-Directed Learning Readiness Scale for Nursing Education (SDLRSNE), Self-Regulated Learning Scale (SRL), Autonomous Learning Competencies scale (ALC), and Competencies of Autonomous Learning of Nursing Students (CALNS). Overall scores and subgroup analyses with the SRL were all in favor of the FC. Conclusions: The result of this meta-analysis indicated that FCs could improve the effect of self-directed learning in nursing education. Future studies with more RCTs using the same measurement tools are needed to draw more authoritative conclusions.