While sarcopenia is associated with adverse pancreatic cancer (PC) outcomes, prospective evidence linking muscle health to PC risk remains limited. This study aimed to prospectively investigate the associations of grip strength and muscle mass with incident PC risk in the UK Biobank cohort.Among 363,693 UK Biobank participants, grip strength (kg) and bioelectrical impedance analysis (BIA)-derived muscle mass (weight-normalized) were measured. Cox proportional hazards models, adjusted for age, sex, lifestyle factors, and metabolic syndrome components, assessed PC risk over a median 13.7-year follow-up.Higher muscle mass (HR = 0.86, 95% Confidential Interval [CI]:0.78-0.95) and grip strength (HR = 0.90, 95% CI:0.83-0.98) demonstrated linear inverse associations with PC risk showing sex-specific divergence: muscle mass reduction conferred stronger protection in men (HR = 0.84, 95% CI:0.74-0.96), whereas grip strength showed greater impact in women (HR = 0.84, 95% CI:0.74-0.96). Subgroup analyses revealed that improved grip strength reduced PC risk in diabetics (HR = 0.89, 95% CI:0.80-0.99), while obese individuals benefited from both enhanced grip strength (HR = 0.95, 95% CI:0.90-0.99) and muscle mass (HR = 0.88, 95% CI:0.82-0.94). Population-attributable fraction estimates suggest 5-12% of PC cases could be prevented through muscle health interventions.These findings highlight an association between improved physical capability and reduced PC risk, supporting the adoption of sex-specific preventive strategies-prioritizing muscle mass augmentation in men and grip strength enhancement in women, particularly in high-risk metabolic subgroups. By characterizing sarcopenia as an independent risk factor, this study underscores the imperative to integrate muscle preservation into pancreatic cancer prevention paradigms.© 2025. The Author(s).