Background: Heart failure is a leading cause of hospitalization among adults in the United States. Nurse-led interprofessional clinics have been shown to improve heart failure outcomes in patients with heart failure, specifically decreasing readmission rates. Yet, there is little information on the impact of nurse-led interprofessional collaborative practice within an underserved population with heart failure. Thus, the purpose of this study was to compare the differences in readmission days and cost in patients followed by an interprofessional collaborative practice clinic (both engaged and not engaged) and those who did not establish care with the clinic. Methods and Results: Demographic, clinical, and readmission data were compared among patients with heart failure (59% African American; 72% male; mean age, 49 years) stratified into 3 groups: engaged patients (n = 170), not-engaged patients (n = 103), and not-established patients (n = 111) who had an initial appointment to clinic but did not establish care. Patients with 6 months of data before and after the scheduled clinic visit were included in the study. Differences in baseline characteristics, frequency and length of hospital admissions, and costs were analyzed using analysis of variance, Wilcoxon matched-pairs testing, multivariate analysis of variance, logistic regression, and financial analytics. Overall, the number of inpatient hospital days decreased in the engaged group compared with those in the not-engaged and not-established groups (P < .001). The total cost savings were significantly greater in the engaged group ($1,987,379) (P < .001). Conclusions: The findings of this study may steer health care providers to incorporate interprofessional collaborative practice into heart failure management with a particular focus on underserved populations.