INTRODUCTION: Acute postoperative pain following major surgery has come under increasing scrutiny as a harbinger for the development of potentially debilitating chronic postsurgical pain (CPSP), which is defined as the new onset of pain or intensification of presurgical pain persisting at least two to three months following surgery. We examined the prevalence of and risk factors associated with CPSP among women undergoing breast reconstruction. METHODS: Women ≥18 years undergoing immediate or delayed post-mastectomy breast reconstruction were recruited as part of the NCI-funded Mastectomy Reconstruction Outcomes Consortium Study, a prospective cohort study including 10 centers across the U.S. and Canada. In the current analysis, women were assessed preoperatively and at two-years postoperatively for pain experience (NPRS, MPQ-SF), severity of anxiety (GAD-7), and depression (PHQ-9), relevant medical/surgical variables, and reconstructive procedure type. Mixed-effects regression modeling was used to assess the relationship between patient-specific factors as the independent variables and two-year postoperative pain. RESULTS: Of the 1,996 patients included in the analysis, 92.7% (n=1851) underwent immediate reconstruction, with the majority (n=1263, 63.3%) choosing tissue expander-implant (TE/I) reconstruction. There was no significant difference between women reporting moderate or severe pain at two-year follow-up compared to preoperatively (11 vs. 10%, p=0.083). Regression modeling indicated that both preoperative pain (p<0.001) and depression severity (p<0.004) were related to CPSP. Autologous flap reconstruction was associated with more severe CPSP than TE/I on the MPQ-Sensory and Affective ratings. BMI, bilateral reconstruction, axillary lymph node dissection, and adjuvant radiation and chemotherapy were associated with CPSP for at least one pain measure. CONCLUSION: Women undergoing autologous reconstruction had significantly greater pain levels on the MPQ compared to TE/I patients two-years postoperatively, an important point to consider during preoperative counseling. The presence of preoperative pain was also a risk factor for CPSP. While multiple studies in recent years have focused on the widespread and under-reported prevalence of post-mastectomy CPSP, only 10% of the sample had moderate-to-severe pain at two years. Therefore, approximately 90% were either pain-free or living with a level of pain that would not be expected to interfere with daily function. Overall, our data suggest that CPSP for this cohort may be of less clinical concern than previously described, and reports of persistent pain after breast reconstruction may not necessarily reflect surgery-induced pain.