Breast anesthesia after mastectomy and reconstruction has been an ongoing concern with few improvements made in recent years. At present, there is a lack of studies evaluating the impact of comorbidities on sensation restoration. Identifying risk factors (RF) will be helpful with preoperative counseling.This was a prospective study on patients who underwent mastectomy and immediate implant-based or neurotized deep inferior epigastric perforator (DIEP) flap-based reconstruction. Neurosensory testing was performed at predefined time points using a pressure specified device. Patients were stratified based on reconstruction type and comorbidities, including obesity (≥30 kg/m2), age (>55 years), hypertension, alcohol use, and smoking status. Sensory comparisons among the comorbidity groups were conducted using unpaired 2-sample t tests.A total of 239 patients were included in this study with 109 patients in the implant cohort and 131 patients in the DIEP cohort. One patient underwent bilateral reconstruction using both reconstructive modalities. Preoperatively, age older than 55 years was identified as an RF for reduced breast sensation in the implant cohort (difference in threshold, 10.7 g/mm2), whereas obesity was identified as an RF in the DIEP cohort (difference in threshold, 8 g/mm2). During the first 2 years postreconstruction, age older than 55 years and tobacco use history were found to be negatively correlated with breast sensation for both cohorts. With DIEP reconstruction specifically, obesity was identified as an additional RF during the early postoperative period. Of note, none of the comorbidities were found to be long-term RFs for reduced breast sensitivity. All breast sensation levels returned to comparable levels across all comorbidities by 4 years postreconstruction.Currently, various comorbidities have been recognized as RFs for several postoperative complications including extended postoperative stay, necrosis, infection, and reoperation. However, our findings suggest that, although age, smoking history, and obesity showed transient associations with reduced breast sensation during the initial years postreconstruction, they play no role in the long-term potential of sensory nerve regeneration.