There is limited information on the influence of a patient's comorbid status on the type of immediate breast reconstruction (IBR) selected. Our aim was to provide a population-based review of the relationship between baseline comorbid conditions and IBR subtype selected. This is a retrospective cohort study using the National Surgical Quality Improvement Program database to identify IBR recipients. Multivariable regression analyses was performed to identify the association between comorbidity and IBR subtype selection (prosthetic, pedicled, and free autologous). A total of 48,096 mastectomy patients were identified, of which 17,404 patients received IBR. IBR patients were younger (51 ± 10.4 versus 61.5 ± 13.6 years) and had a lower body mass index (27.1 ± 6.4 versus 28.9 ± 7.3) relative to patients who did not pursue IBR (p < 0.001 for all). Overall, IBR patients had a significantly lower incidence of comorbid conditions. In adjusted models, patients aged 45-64 years were more likely to pursue pedicled-autologous reconstruction (OR: 1.43, p < 0.001) and those older than 65 years were less likely to undergo free-autologous reconstruction (OR: 0.64, p = 0.02). Class I and II obesity was associated with pedicled (class I OR: 1.57, class II OR: 1.41) and free transfer (class I OR: 1.81, class II OR: 1.66) autologous IBR utilization (all p < 0.001). Also, smoking was related to increased chance of prosthetic reconstruction while preoperative radiotherapy was linked to free-autologous IBR. IBR patients were noted to be healthier than their non-IBR counterparts, and each IBR subtype was associated with a particular comorbidity profile. This has significant implications with regard to creation of an IBR-predictive model. Such a tool will improve preoperative counseling and decision making.