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Association of Physical Activity and Obesity With the Risk of Degenerative Cervical Myelopathy. BACKGROUND AND OBJECTIVES: Information about modifiable risk factors for degenerative cervical myelopathy (DCM) remains lacking. Although physical activity (PA) is a known risk factor for many chronic conditions, its role in DCM risk has not been studied. Therefore, this study investigated the association between PA and DCM risk. METHODS: This was a retrospective analysis of data prospectively collected from the UK Biobank, with baseline assessments between 2006 and 2010. Participants were followed for a median duration of 13.8 years, with follow-up extending through 2022. PA was measured by self-reported questionnaires (International Physical Activity Questionnaire expressed as metabolic equivalent task minutes/week) and by accelerometer [mean acceleration and proportion of time spent in light and moderate-to-vigorous physical activity (MVPA)]. The primary outcome was the subsequent development of DCM. Cox proportional hazards models assessed associations between PA and DCM risk using IQR increase, with the 25th percentile as reference. Mediation analyses evaluated the role of body mass index (BMI). RESULTS: In total, 357 056 participants (342 166 with self-reported PA and 84 762 with accelerometer-measured PA) were included. The mean patient age was 56.65 years, 53.03% were female, and 95.0% were White. Self-reported overall activity [hazard ratios (HR), 0.87; 95% CI: 0.82-0.93], MVPA (HR, 0.90; 95% CI: 0.85-0.96), and light activity (HR, 0.89; 95% CI: 0.84-0.95) were each inversely associated with DCM. In the accelerometer cohort, participants at the 75th percentile of mean acceleration had a 30% lower risk of DCM (HR, 0.70; 95% CI: 0.52-0.94) compared with those at the 25th percentile. Greater MVPA time was similarly associated with reduced DCM risk (HR, 0.81; 95% CI: 0.67-0.97). BMI partially mediated the association between PA and DCM. CONCLUSION: Higher PA levels were associated with reduced DCM risk, partially mediated through lower BMI. These findings highlight the potential of PA and BMI as modifiable risk factors for DCM.