Retinal venous occlusion represents a common retinal disorder that untreated often leads to severely reduced vision. While general risk factors for vascular disease are known to increase the risk of an event, the role of thrombophilia is controversial. The purpose of this systematic review was to evaluate the evidence for thrombophilia investigation in patients presenting with retinal venous occlusion. Eligible studies were identified by a MESH-based search in PubMed 11-13 of March 2015. The level of evidence was stated according to the guidelines published by the GRADE working group using three levels for quality of evidence: high, moderate and low. A total of 118 studies relating to the study question were identified. After excluding case stories, commentaries, cross-sectional studies and reviews/expert opinions, 28 original papers and two meta-analyses were included in the final qualitative synthesis. The majority of studies were small case-control studies, and only one large cohort study was identified. No randomized controlled trials were retrieved. All the studies were categorized as low quality of evidence. Systematic thrombophilia screening in patients presenting with retinal venous occlusion cannot be recommended.