This large population‐based study compared breast‐conserving surgery with radiation therapy (BCT) with mastectomy on (long‐term) breast cancer‐specific (BCSS) and overall survival (OS), and investigated the influence of several prognostic factors. Patients with primary T1‐2N0‐2M0 breast cancer, diagnosed between 1999 and 2012, were selected from the Netherlands Cancer Registry. We investigated the 1999–2005 (long‐term outcome) and the 2006–2012 cohort (contemporary adjuvant systemic therapy). Cause of death was derived from the Statistics Netherlands (CBS). Multivariable analyses, per time cohort, were performed in T1‐2N0‐2, and separately in T1‐2N0‐1 and T1‐2N2 stages. The T1‐2N0‐1 stages were further stratified for age, hormonal receptor and HER2 status, adjuvant systemic therapy and comorbidity. In total, 129,692 patients were included. In the 1999–2005 cohort, better BCSS and OS for BCT than mastectomy was seen in all subgroups, except in patients < 40 years with T1‐2N0‐1 stage. In the 2006–2012 cohort, superior BCSS and OS were found for T1‐2N0‐1, but not for T1‐2N2. Subgroup analyses for T1‐2N0‐1 showed superior BCSS and OS for BCT in patients >50 years, not treated with chemotherapy and with comorbidity. Both treatments led to similar BCSS in patients <50 years, without comorbidity and those treated with chemotherapy. Although confounding by severity and residual confounding cannot be excluded, this study showed better long‐term BCSS for BCT than mastectomy. Even with more contemporary diagnostics and therapies we identified several subgroups that may benefit from BCT. Our results support the hypothesis that BCT might be preferred in most breast cancer patients when both treatments are suitable. What's new? While breast‐conserving therapy (BCT) and mastectomy have long been considered equivalent in terms of survival in early‐stage breast cancer, recent studies suggest BCT offers superior survival over mastectomy. The findings of this study support that idea, showing that breast cancer‐specific survival and overall survival were greater for BCT than mastectomy in analyses of 129,692 patients diagnosed with breast cancer in The Netherlands between 1999 and 2012. Subgroup analyses revealed better survival for BCT in most instances, with survival being similar for BCT and mastectomy primarily among patients under age 50, patients without comorbidity, and those treated with chemotherapy.