OBJECTIVES:  PREAMBLE (NCT01838512) is an international cohort study on the real-world effectiveness of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs) and combination therapy for RRMM. Here, we compare HCRU data from EU (Italy, France, UK, Germany) and US cohorts. METHODS:  Eligible patients: age ≥18y, RRMM (≥1 prior therapy) and initiated treatment with IMiD, PI or IMiD+PI 90 days prior/30 days after enrollment. Data were collected at healthcare provider (HCP) visits. RESULTS:  At data cut-off (April 2016), 572 EU patients and 267 US patients (median age 69 and 67y, respectively) were on treatment. Characteristics (EU/US): median follow-up, 15.8/19.7 months; refractory disease at study entry, 21%/25%; prior therapies >3, 16%/18%; prior transplantation, 45%/55%. Median time from diagnosis to index therapy was 40 months, EU and 41 months, US. MM therapy (EU/US): IMiD as index therapy, 334 (58%)/71 (27%) patients, mostly lenalidomide (85%/55%); PI, 228 (40%)/147 (55%), mostly bortezomib (97%/52%); combination therapy, 10 (2%)/49 (18%). Median duration (months) on index therapy varied across treatments (EU/US): IMiD, 9.9/9.8; PI, 4.9/5.9; IMiD+PI, 2.8/4.0. Most common switch from index therapy was PI to IMiD: EU 52% (57/110), US 38% (31/82). Median (Q1–Q3) number of HCP visits during Y1: EU 4 (0–20), US 4 (1–16). In Y2+3, number of visits was EU patients: 2 (0–12), US patients: 1 (0–11). Main HCP visit type differed: hospital outpatient, EU (64%); clinic/physician’s office, US (87%); MM management was main reason for visit: EU 92%, US 85%. Hospitalizations accounted for 6% of HCP visits overall; main reason MM management (EU 66%, US 64%). Overall visits for treatment-related AE management: EU 8%, US 14%. CONCLUSIONS:  Disease progression and routine MM management are the main HCRU drivers in EU and US. Early use of novel therapies, with potential to provide durable responses, could improve MM management and patient outcomes. Cost analyses are underway.