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Background/Objectives:BCR::ABL1-negative myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are clonal hematopoietic stem cell disorders characterized by chronic systemic inflammation and elevated thrombotic risk. Osteoarthritis (OA), the most prevalent joint disease globally, is common in MPNs and shares a common proinflammatory cytokine milieu with MPNs. However, whether symptomatic OA may independently impact MPN-related symptom burden and thrombotic outcomes remains unexplored. Methods: In this prospective two-center study conducted in Croatia (2021-2023), 107 consecutive MPN patients diagnosed by 2016 World Health Organization criteria underwent orthopedic evaluation and completed the MPN Symptom Assessment Form (MPN-SAF) at enrolment. Symptomatic OA was defined as radiographic grade ≥1 (Kellgren-Lawrence) with concordant symptoms. Patients were subsequently followed for thrombotic events. Multiple linear regression and Cox proportional hazards regression were used for multivariable analyses. Results: Symptomatic OA was identified in 64 patients (59.8%). The total symptom score (TSS) was significantly higher in OA patients (p < 0.001), and in multivariable analysis, OA independently predicted higher TSS (β 10.12, 95% confidence interval-CI 5.38-14.86, p < 0.001), alongside female sex and arterial hypertension. Over a median follow-up of 44 months, 10 thrombotic events occurred. Patients with symptomatic OA had significantly worse time to thrombosis (hazard ratio-HR 3.61, 95% CI 1.02-12.8, p = 0.046). In multivariable Cox regression, OA remained associated with thrombosis (HR 15.55, p = 0.002), while female sex (HR 0.17, p = 0.042) and aspirin use (HR 0.15, p = 0.019) were protective. Conclusions: Symptomatic OA may be associated with higher symptom burden and, in this preliminary analysis, with higher thrombotic risk in MPNs. These findings support systematic OA evaluation in MPNs and multidisciplinary management strategies targeting this frequent and burdensome comorbidity.