Background Change in low-density lipoprotein cholesterol (LDL-C) level after statin initiation varies widely among individuals, and in part may be because of factors shared by family members. Methods and Results We used the Danish national registers to identify 89 006 individuals who initiated statins between 2008 and 2018 and had LDL-C measured immediately before and after the start of treatment. Among these, we identified 5148 first-degree relatives and 3198 spouses. We decomposed the variation in attained LDL-C level after statin initiation by applying a mixed-effect model with 5 variance components (inter-family and inter-individual variance in pre-statin LDL-C level, inter-family and inter-individual variance in statin response, and residual variance). Results were presented as a percentage of the total variance explained by the different variance components. We found that half of the variation in attained LDL-C level after statin initiation consisted of variance in statin response, approximately one third of variance in pre-statin LDL-C level, and the remaining 10% to 15% of residual variance. While the inter-individual variance in statin response accounted for almost half of the LDL-C variation in both cohorts, the inter-family variance in statin response accounted for 3.3% among first-degree relatives and for 6.0% among spouses. Conclusions Individual factors account for most of the variation in LDL-C level after statin initiation; factors affecting statin response common within spouses and first-degree relatives account for a similar share of variation. These results suggest a modest influence of shared genetics and shared familial environment on statin response.