Two-stage tissue expander/implant (TE/I) and deep inferior epigastric perforator (DIEP) flaps are the two main pillars of breast reconstruction. This study aimed to conduct a longitudinal analysis of long-term outcomes after immediate DIEP- and TE/I-based reconstruction. This retrospective cohort study included patients with breast cancer who underwent immediate DIEP- or TE/I-based reconstruction between 2012 and 2017. The cumulative incidence of major complications, defined as unplanned reoperation/readmission due to complications, was analyzed by the reconstruction modality and its independent association. In total, 1,474 cases (1,162 TE/I and 312 DIEP cases) were analyzed, with a median follow-up of 58 months. The 5-year cumulative incidence of major complications was significantly higher in the TE/I group (10.3% vs. 4.7%). On the multivariable analyses, the use of DIEP flap was associated with a significantly reduced risk of major complications compared to that of TE/I. A more prominent association was observed in the analysis of patients who received adjuvant radiotherapy. Restricting analysis to those who received adjuvant chemotherapy revealed no differences between the two groups. The rate of reoperation/readmission for improving aesthetic outcomes was similar in the two groups. Long-term risks for unexpected reoperation/readmission may differ between DIEP- and TE/I-based immediate reconstruction.