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Background Patients with peripheral artery disease (PAD) and coexisting diabetes mellitus (DM) have greater PAD progression and adverse limb events. Our aim was to study whether PAD-specific health status differs by DM. Methods and Results The PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) trial is a 16-center international registry that includes patients with recent exacerbations or new-onset symptomatic PAD presenting to specialty clinics. We assessed PAD-specific health status initially and at 3, 6, and 12 months (Peripheral Artery Questionnaire [PAQ]). We used hierarchical, multivariable, linear regression, and repeated measures analyses to study the association between DM and baseline health status initially and over 3 to 12 months. Models were adjusted for demographics, socioeconomic factors, PAD severity, comorbidities, and psychosocial characteristics. The interaction of DM with PAD revascularization on 3- to 12-month health status was also tested. Of 1204 patients, 398 (33%) had DM (94% type 2). Patients with versus those without DM had lower unadjusted PAQ summary scores at baseline and 3, 6, and 12 months (46.1 versus 50.8, 63.6 versus 68.2, 65.7 versus 71.7, and 65.4 versus 72.6; P ≤0.01). In fully adjusted models, the effect of DM on baseline (mean difference, -0.65; 95% CI, -2.86 to 1.56 [ P =0.56]) and over 3- to 12-month PAQ summary scores (mean difference, -1.59; 95% CI, -4.06 to 0.88 [ P =0.21]) was no longer significant. Twelve-month health status gains following revascularization were similar in both groups ( P =0.69). Conclusions Patients with PAD with coexisting DM have poorer health status, mostly explained by the differences in their psychosocial and other comorbidity burden. Patients with PAD and DM versus those without DM experience similar health status benefits following PAD revascularization.