OBJECTIVES: To evaluate colesevelam treatment persistence and associated factors METHODS: In this retrospective study, patients with hyperlipidemia (HL) diagnosis were identified through electronic health records, who were ≥18 years old, had an initial order for colesevelam between January 2004 and December 2011, an LDL-C value within 3 months of the initial order date (baseline), and ≥12 months of LDL-C follow-up.  Colesevelam treatment persistence was defined a priori as no order gap >30 days. Multivariate stepwise logistic regression was performed to assess clinical and patient-level factors associated with ≥12 months of colesevelam treatment persistence. Adjusted odds ratios (OR) and corresponding 95% confidence intervals (CIs) were calculated. A p-value <0.05 was considered statistically significant. RESULTS: A total of 971 patients met the predefined inclusion criteria, of which 48.2% had ≥12 months of persistent treatment. Multivariate analysis showed that female sex (OR: 0.68; 95% CI: 0.53, 0.88; p=0.004) and concurrent insulin therapy (0.65; 0.46, 0.94; p=0.021) were associated with a lower odds of having ≥12 months colesevelam treatment persistence, whereas an increased number of concomitant medications (1.09; 1.01, 1.19; p=0.023) and concurrent intestinal cholesterol absorption inhibitor therapy (1.51; 1.08, 2.11; p=0.016) was associated with a greater odds of having ≥12 months treatment persistence. CONCLUSIONS: Several factors were significantly associated with colesevelam treatment persistence among patients with HL in an integrated health system. In particular, concomitant medication was associated with better treatment persistence; these data may assist in optimizing therapy regimens for lipid management.