Objective To systematically review the effectiveness and safety of arsenic trioxide (ATO) versus retinoic acid for patients with acute promyelocytic leukemia (APL). Methods Such databases as PubMed, The Cochrane Library (Issue 12, 2012), CNKI, WanFang Data and VIP were electronically and comprehensively searched from inception to December 2012, for randomized controlled trials (RCTs) on the effectiveness and safety of ATO versus retinoic acid for patients with APL. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Then, meta-analysis was performed using RevMan 5.0.2 software. Results Eight RCTs involving 586 cases of APL patients. The results of meta-analysis showed that, ATO and all-trans-retinoic (ATRA) were not statistically different in CR rates (OR=0.85, 95%CI 0.54 to 1.35, P=0.50), CR time (OR=–8.14, 95%CI –16.42 to 0.13, P=0.05), recurrence rates (OR=0.14, 95%CI 0.02 to 1.21, P=0.07), early mortality (OR=0.82, 95%CI 0.32 to 2.06, P=0.67), and five-year total survival rates (OR=1.19, 95%CI 0.54 to 2.60, P=0.66). ATO had lower incidences of adverse reaction such as hyperleukocytosis syndrome (OR=0.32, 95%CI 0.18 to 0.58, P=0.000 1) and retinoic acid syndrome (OR=0.05, 95%CI 0.02 to 0.14, Plt;0.000 01). Conclusion ATO and ATRA are alike in CR rates, CR time, recurrence rates, early mortality, and five-year total survival rates, but ATO causes less adverse reaction. Due to the limited quantity and quality of the included studies, ATO should be applied with caution according to patients’ conditions in clinic.