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Summary: Background: Synovitis has long been considered a common and modifiable inflammatory feature of osteoarthritis (OA), but current disease-modifying anti-inflammatory treatments appear ineffective in OA clinical trials. Elucidating the temporal relationship between synovitis and OA could provide insight into the role of synovitis in OA. Methods: We conducted a prospective cohort study based on the baseline and three-year follow-up data from the Xiangya Osteoarthritis (XO) Study. We assessed bidirectional associations between ultrasound-detected synovitis and radiographic and symptomatic OA at knee and hand sites using generalized estimating equations. Additionally, we performed bidirectional Mendelian randomization (MR) analyses to test these hypotheses utilising whole-genome sequencing data in the XO population. Age, sex, body mass index, smoking, alcohol consumption, educational level, physical activity, and joint injury history were adjusted for these analyses. Findings: A total of 2211, 2420, 2280, and 2600 participants were enrolled for analyses of radiographic knee OA (RKOA), symptomatic knee OA (SKOA), radiographic hand OA (RHOA) and symptomatic hand OA (SHOA), respectively. The baseline synovitis (i.e., with synovitis vs. without synovitis) was associated with the incident RKOA (76/277 vs. 557/3674 knees), SKOA (49/387 vs. 287/4213 knees), RHOA (171/358 vs. 686/3664 hands) and SHOA (35/689 vs. 76/4327 hands), with adjusted odds ratio (aORs) of 2.2 (95% CI 1.7–3.1), 2.0 (1.3–2.9), 3.4 (2.7–4.4), and 2.4 (1.5–3.8), respectively. The baseline RKOA (with OA vs. without OA: 409/1246 vs. 481/3758 knees), SKOA (200/576 vs. 675/4356 knees), RHOA (192/778 vs. 410/3723 hands), and SHOA (41/162 vs. 548/4285 hands) were also associated with the incident synovitis, with aORs of 3.4 (95% CI 2.9–4.1), 2.7 (2.1–3.4), 2.3 (1.8–2.9) and 1.9 (1.2–2.8), respectively. These bidirectional associations were stronger when more active synovitis was compared with the reference group (all P