Background: Previous work identified a direct relationship between frailty and adverse outcomes in cardiac surgery, but assessment of the effect across subgroups of patients has largely been ignored. This study identified whether the association of frailty (measured by gait speed) with adverse outcomes differed across subgroups of patients. Methods: The study evaluated 53,932 patients who underwent cardiac operations between 2011 and 2016 across 33 Michigan institutions. Five-meter gait speed (in seconds) was divided into groups: faster (<5.0 seconds), intermediate (5.0 to 5.99 seconds), and slower (≥6.0 seconds). The study used mixed logistic regression to estimate the relationship between increasing gait speed time and a patient's odds of major morbidity or mortality, by adjusting for patient-related demographics, disease characteristics, surgeon, and hospital. Effect modification by subgroup of patients and gait speed test time was tested with interaction terms. The study's secondary end point was an analysis of discharge disposition. Results: Nearly one fourth (22.7%) of patients had at least one gait speed test. Slower (34% of patients) versus faster (28%) patients were older (72.5 years vs 62.6 years), had more comorbidities, and had the primary outcome (16.6% vs 9.5%) (p < 0.0001). Significant interactions with gait speed existed for patients’ comorbidities (chronic lung disease, atrial fibrillation, p < 0.05), although marginal interactions existed for patients’ age (p = 0.059) and diabetes (p = 0.063). Slower patients were more often discharged to a facility rather than home. Conclusions: Slower gait speed was associated with increased odds of major morbidity or mortality. This effect was amplified among patients with preexisting comorbidities. Future studies should evaluate the impact of preprocedural interventions on frailty, including those aimed at addressing comorbidities.