Background: Caregivers of patients with cancer play a critical role in supporting patients when making informed decisions about their medical care. Although MM patients and their caregivers face an incurable illness, data describing caregiver perceptions of the patient’s prognosis and factors associated with accurate prognostic perceptions are lacking. Methods: We conducted a cross-sectional, multisite study of caregivers of MM patients between 6/2020-1/2021. Eligible caregivers were identified by the patient as the primary caregiver and enrolled in 1 of 3 cohorts based on lines of therapy: 1) caregivers of newly diagnosed patients receiving first-line therapy; 2) 2-3 lines; 3) ≥4 lines. Caregivers completed the Perception of Treatment and Prognosis Questionnaire to assess their perceptions of the illness and prognosis. We also used the CareGiver Oncology Quality of Life (QOL) questionnaire, the Hospital Anxiety and Depression Scale, the Post-Traumatic Stress Disorder Checklist–Civilian Version, and the Brief COPE to assess caregiver QOL, psychological distress, and coping strategies. We used a multivariate logistic regression analysis to examine whether caregiver factors (i.e. demographics), line of therapy, QOL, psychological distress, or coping were associated with caregiver perceptions of the patient’s prognosis. Results: We enrolled 113 caregivers of MM patients (newly diagnosed (n=39), 2-3 lines (n=37), and ≥ 4 lines (n=37)). Overall, 89.2% (99/111) of caregivers reported that it is ‘extremely’ or ‘very’ important to know about the patient’s prognosis and the majority (58.0%, 65/112) stated that they had received adequate information regarding the patient’s prognosis. Caregivers reported that prognostic information was ‘extremely’ or ‘very’ helpful in making decisions about treatment (93.3%, 97/104), preparing for the future (88.2%, 90/102), and coping with the disease (85.6%, 89/104). Most caregivers (84.7%, 94/111) reported that the oncologist told them the patient’s cancer was incurable. In contrast, only 53.6% (59/110) of caregivers reported that they thought the patient’s cancer was incurable and 48.6% (52/107) acknowledged that the patient is terminally ill. In a multivariate analysis, we found that the use of positive reframing coping (OR=0.71, 95%CI=0.52-0.97, P=0.033) was associated with lower odds of reporting an accurate perception of prognosis. Caregiver demographics, line of therapy, QOL, and psychological distress were not associated with their perceptions of the patient’s prognosis. Conclusions: Although the majority of caregivers of MM patients report that knowing the patient’s prognosis is extremely important, a substantial minority still have significant misperceptions of the patient’s prognosis. Interventions are needed to promote effective coping and enhance caregiver perceptions of the patient’s prognosis to facilitate informed decision-making in this population.