OBJECTIVES: Robust associations between lipoprotein(a) [Lp(a)] and cardiovascular events (CVE) have been noted in previous studies conducted in general population.  However, the relationship between Lp(a) and subsequent CVE is uncertain especially among high cardiovascular risk patients.  This was investigated in a systematic review. METHODS: Published systematic review methodology, including extensive literatures searches were used to identify prospective studies, which assessed the relationship between Lp(a) levels and CVE, using multivariable analyses. Additional information was gathered on Lp(a) assays (e.g. isoform independence), model variables (including LDL-C levels) and population characteristics (e.g. race). RESULTS: Searches of electronic databases (e.g. MEDLINE and EMBASE), conference abstracts, and grey literature up to February 2015, retrieved 2,472 records. From these 53 studies (102 citations) were included.  The overall level of bias across the studies was moderate, as assessed using the Quality in Prognostic Studies (QUIPS) tool.  The studies used varied CVE outcomes and multivariable models. Heterogeneity was evident in the assessment of Lp(a) values. LDL-C was included as a variable in 17 studies; 16 reported a significant positive correlation between Lp(a) and CVE.   Across the 36 primary prevention studies in the general population (hazard ratios ranged from 1.16 to 2.97) and the six primary prevention studies in high risk patients (hazard ratios ranged from 1.21 to 3.7), there was evidence of a statistically significant relationship between increased Lp(a) and an increased risk of future CVD.  Evidence in secondary prevention populations (11 studies) was also suggestive of a modest statistically significant relationship (hazard ratios ranged from 0.75 to 3.7). CONCLUSIONS: There is evidence to suggest that increased Lp(a) levels are associated with an increase in CVE in high-risk populations.  However, heterogeneity hampers the interpretation of evidence across specific populations. Further studies are warranted to investigate CVE reduction by therapies aimed at lowering Lp(a) levels among high risk patients.