To assess the levels of receptor activator of NF-κB ligand (RANKL) in serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to correlate its levels with disease activity and severity. Serum and SF levels of RANKL were measured in 24 patients with RA (Group I) and 20 patients with OA (Group II); patients were selected according to the ACR criteria, and serum RANKL was measured in 13 healthy controls. All patients were subjected to full rheumatological assessment. In RA group, serum level of RANKL was significantly higher than control group (P = 0.01), but not correlated with disease activity and severity parameters apart from number of tender joints (P = 0.03). SF level of RANKL was significantly correlated with disease duration (P = 0.02), number of tender (P = 0.002) and swollen joints (P = 003), ESR (P = 0.01), CRP (P = 0.000), DAS-28 (P = 0.004), and SENS (P = 0.03). In patients with OA, serum level of RANKL was significantly higher than the control group (P < 0.001), and it was statistically insignificant with clinical, laboratory, or radiological data, while SF level of RANKL was statistically significantly higher in patients with Heberden and Bouchard nodes (P = 0.007), Kellgren-Lawrence score (P = 0.002), and with the erosive changes of hands (P = 0.006). The mean serum RANKL in RA group was insignificant with that of total OA group. SF level of RANKL was significantly higher in RA than erosive OA patients and in erosive than non-erosive OA with (P = 0.001, in each one). The SF level of RANKL is an important marker of both disease activity and severity in RA patients; while in OA patients, it is an important marker of disease severity especially in erosive than non-erosive types. Serum level of RANKL may be of low benefit in disease activity and severity of both rheumatoid arthritis and osteoarthritis.