Background: This study aimed to evaluate the prognostic value of the ratio of involved to uninvolved free light chain (rFLC) levels and lactic dehydrogenase (LDH) levels in the risk stratification of patients with multiple myeloma (MM). Materials and Methods: Clinical data of 283 patients with newly diagnosed MM were retrospectively analyzed. Results: In the traditional chemotherapy group, patients with an rFLC < 100 had a better prognosis than those with an rFLC >= 100 (40 months versus 6 months, P = 0.022), as did patients with an LDH <= upper limit of normal (ULN) compared to those with an LDH > ULN (29 months versus 6 months, P = 0.023). In patients who underwent novel drug-combined therapy, no significant difference was observed between the rFLC < 100 group and the rFLC > 100 group (54 months versus median not reached, P = 0.508). However, patients with an LDH <= ULN had a better prognosis than those with an LDH > ULN (60 months versus 21 months, P = 0.004). Using an rFLC >= 100 and an LDH >= ULN as adverse risk factors, patients were classified into 3 groups: group 1 (no adverse risk factors), group 2 (1 adverse risk factor) and group 3 (2 adverse risk factors). The median overall survival (OS) of groups 1, 2 and 3 was 52 months, 34 months and 15 months, respectively (P = 0.001). Conclusions: rFLC and LDH levels were sensitive prognostic factors in MM patients, combining them could improve the risk stratification and treatment choice of patients in clinical practice.