BackgroundThere is an increased concern that statins may have an unintended effect of elevated lipoprotein(a) [Lp(a)]. We conducted a large sample real-world study to test the association.MethodsThis retrospective cohort study was conducted using data from an integrated SuValue database, which includes 221 hospitals across China covering more than 200,000 of population with longitudinal follow-up to 10 years. Propensity score matching was applied to identify two comparable cohorts with statin users and non-statin users. Detailed follow-up information such as Lp(a) levels were extracted. The hazard ratio was calculated on Lp(a) changes based on the statin usage cohorts. Detailed subgroup and different characteristic cohorts’ analyses were also conducted.ResultsAfter baseline propensity score matching, a total of 42,166 patients were included in a 1:1 matched ratio between statin users and non-statin users. In the case of no difference in low density lipoprotein (LDL-C), Lp(a) was increased significantly with the use of statins (adjusted HR 1.47; 95% confidence interval [CI] 1.43–1.50). Lp(a) increase was observed in various subgroup analyses and different cohorts. The dose intensity of statin was positively associated with the evaluated Lp(a) level.ConclusionThe use of statins was associated with an increased risk of Lp(a) elevation compared with non-statin use counterparts. The clinical relevance of these increases needs to be addressed in surrogate marker trials and/or large, cardiovascular outcomes trials.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40001-023-01155-x.