To evaluate the prognostic value of bone marrow (BM) imaging pattern and other imaging findings assessed by 18F-FDG PET-CT in multiple myeloma(MM) and to find out the image interpretation cut-off to define different BM tracer uptake pattern. We retrospectively studied PET-CT examinations and clinical data of 100 healthy individuals and 172 newly diagnosed MM patients. A BM uptake > liver SUVmean was selected as the positivity cut-off of pathological uptake in BM after comparing BM uptake in normal control and MM patients. With this interpretation cut-off, we defined the BM FDG uptake pattern as four types: normal, focal, diffuse, and mixed. The clinical correlation and prognostic value of BM uptake pattern were evaluated. The findings were validated in an independent prospective cohort with 72 MM patients. In MM cohort, 34.9% patients had focal BM uptake pattern, 3.5% had diffuse pattern, 38.4% had mixed pattern, and 23.3% had normal BM uptake. Diffuse/mixed pattern was correlated with clinical and imaging parameters indicating high tumor burden, and inferior progression free survival (PFS; 3-year-PFS 26.8%) and overall survival (OS; 3-year-OS 50.6%). BM uptake pattern was an independent prognostic factor and diffuse/mixed pattern was associated with inferior OS (P = 0.037, HR 7.16) and PFS (P = 0.015, HR 7.77). The prognostic value of BM uptake pattern was also confirmed in validation set. We propose an FDG uptake higher than liver as the positivity cut-off to discriminate between physiological and pathological uptake in BM and defined four BM FDG uptake pattern. BM FDG uptake pattern is a reliable prognostic predictor of MM.