Repository corticotropin injection (RCI) is indicated as adjunctive, short-term therapy in selected patients with RA. To characterize RCI users and identify predictors of RCI initiation in RA, we compared preindex characteristics, treatment patterns, comorbidities, healthcare resource utilization (HCRU), and costs for patients who had initiated RCI treatment (RCI cohort) versus patients with no RCI claims and ≥ 1 targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARD) claim (non-RCI ts/bDMARD cohort). We analyzed pharmacy and medical claims data from a large commercial and Medicare supplemental administrative database. Inclusion criteria were age ≥ 18 years, ≥ 1 inpatient or ≥ 2 outpatient claims with RA diagnosis (January 1, 2007-December 31, 2018), and 12-month continuous medical and pharmacy coverage preindex. Results from baseline cohort comparisons informed multiple logistic regression analysis. Compared with the non-RCI ts/bDMARD cohort (n = 162,065), the RCI cohort (n = 350) had a greater proportion of patients with higher Charlson comorbidity index (CCI) scores; higher mean claims-based index of RA severity and CCI scores; greater frequency of almost all comorbidities; higher use of nontraditional DMARDs, glucocorticoids, and opioids; higher all-cause HCRU; and higher medical and total costs. By multivariable analysis, the most significant predictors of RCI initiation were intermittent glucocorticoid use at any dose (odds ratio [OR] 1.67), extended-use glucocorticoids at medium (OR 2.03) and high doses (OR 2.99), nontraditional DMARD use (OR 2.09), anemia (OR 1.39), and renal disease (OR 2.45). Before RCI initiation, patients had more severe RA, higher comorbidity burden, greater use of glucocorticoids and opioids, and higher HCRU compared with non-RCI initiators. The most significant predictors for starting RCI in patients with RA were intermittent use of glucocorticoids at any dose, extended-use high-dose glucocorticoids, use of nontraditional DMARDs, and comorbid anemia and renal disease.