OBJECTIVES: To examine effectiveness of Colesevelam in reducing low-density lipoprotein cholesterol (LDL-C) among patients with hyperlipidemia (HL) in the real-world setting. METHODS: In this retrospective study, patients with HL were identified through electronic health records, who were ≥18 years old, and had an initial order for colesevelam between Jan 2004 and Dec 2011, an LDL-C value within 3 months of the initial order date (baseline), and ≥12 months of LDL follow-up and continuous colesevelam treatment. Outcome measures were LDL-C and the percent of patients at the appropriate LDL-C goal based on NCEP ATP III guidelines. Generalized estimating equation models were used to assess differences in LDL-C outcome measures between baseline and 12-months follow-up, adjusting for covariates including statin and other medication use. A p-value <0.05 was considered statistically significant. Missing data were imputed by linear interpolation. Sensitivity analysis with and without imputation was performed.   RESULTS: A total of 468 patients met the predefined inclusion criteria and had a mean age of 63 years old. Of these patients, 48.7% were females and 73.3% had prior statin use. Mean change in LDL-C from baseline at 12 months was -11.4 mg/dL (p<0.0001), a relative decrease of 9.6%.  The percent of patients at LDL-C goal at baseline was 42.3%, which increased to 56.2% (p<0.0001) at 12 months. CONCLUSIONS: Long-term, continuous colesevelam treatment was associated with a significant reduction in LDL-C and an increase in the percent of patients achieving LDL-C goal from baseline. This is the first ‘real-world’ analysis demonstrating the benefits of colesevelam among patients with HL in a community-based integrated health system. The LDL-C lowering results parallel findings from pivotal clinical trials.