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Objective Immunosuppressant drugs can increase the risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) and tuberculosis (TB) reactivation. Using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry, we examined pre-treatment screening among new users of biologic or targeted synthetic disease modifying drugs (DMARDs). Methods Data, derived from RISE, included patients ≥ 18 years old who were new users of biologic or targeted synthetic DMARDs. We developed quality measures related to pre-treatment screening for HBV, HCV, and TB in addition to a “composite” measure for all applicable tests. We assessed patient-level screening rates, practice-level variation among practices reporting on ≥ 20 patients, and the frequency of positive results. Results We included 26,802 patients across 213 rheumatology practices nationwide. Patients were 58 (14) years old, 75.9% female; 59.6% had rheumatoid arthritis, and TNFi were the most common index DMARDs (64.9%). Overall, 44.8% and 40.5% patients had any documented HBV or HCV screening, respectively, prior to the index date; 29.7% had TB screening in the year prior to drug start. Only 15.5% had documentation of screening for all appropriate infections prior to drug start. Practice-level performance on the composite measure was low (range 0 to 48.3%). 2.4% of screening tests were positive. Conclusion We found gaps in documentation of key safety measures among practices participating in RISE. Given the small but significant number of patients with active or latent infections that pose safety risks, developing standardized and reliable strategies to capture safety screening measures is paramount.