Abstract: Objectives: The objective of this study was to evaluate the relationship between interleukin-17 (IL-17) serum levels, musculoskeletal ultrasound (MSUS) observations, and clinical disease activity in patients with rheumatoid arthritis (RA) and hand osteoarthritis (OA). Methods: This case–control study involved 120 participants, with 40 individuals assigned to each of the three groups: RA, OA, and control. IL-17 serum levels were quantified in all participants. MSUS of the hand joints was performed on all RA and OA patients. Disease activity in patients with RA was assessed using the Clinical Disease Activity Score (CDAS). Both RA and OA patients completed a Visual Analog Scale (VAS) to evaluate pain intensity. Functional status was evaluated using the Health Assessment Questionnaire (HAQ) for RA patients, while the Australian/Canadian (AUSCAN) Osteoarthritis Hand Index was utilized for OA patients. Results: Serum levels of IL-17 were significantly higher in both the RA and OA groups compared to the control group. Among RA patients, a positive correlation was identified between the CDAS and the VAS for pain. In OA patients, a significant correlation was observed between VAS scores and serum IL-17 levels. Additionally, serum IL-17 levels were associated with the presence of synovitis in both RA and OA groups; however, no significant association was found between IL-17 levels and bony changes such as erosions or osteophytes. In terms of functional evaluation, serum IL-17 levels correlated with HAQ in the RA group, but not with AUSCAN in the OA group. Conclusions: Elevated IL-17 serum levels are linked to inflammatory changes identified by MSUS but not to bony changes. These findings suggest that the rise in IL-17 levels in both OA and RA is primarily driven by underlying inflammatory processes, positioning IL-17 as a potential therapeutic target for both conditions. Keywords: AUSCAN; HAQ; IL-17; MSUS; osteoarthritis; rheumatoid arthritis