Purpose To identify predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer. Patients and Methods We conducted a record-linkage study based on data from Stockholm-Gotland Breast Cancer Register, Swedish Prescribed Drug Register, and self-reported questionnaire. Women diagnosed with breast cancer between 2005 and 2008 in Stockholm, Sweden, were prospectively followed for 5 years until 2013, starting from their first prescription of tamoxifen or aromatase inhibitors (N = 3,395). Results Family history of ovarian cancer (hazard ratio [HR], 1.55; 95% CI, 1.19 to 2.02); younger (< 40 years; HR, 1.39; 95% CI, 1.08 to 1.78) and older (≥ 65 years; HR, 1.15; 95% CI, 1.03 to 1.28) age; higher Charlson comorbidity index (≥ 2 v 0; HR, 1.35; 95% CI, 1.03 to 1.76); and use of analgesics (HR, 1.33; 95% CI, 1.16 to 1.52), hypnotics/sedatives (HR, 1.24; 95% CI, 1.07 to 1.43), GI drugs (HR, 1.25; 95% CI, 1.08 to 1.43), and hormone replacement therapy (HR, 1.27; 95% CI, 1.08 to 1.49) were identified as baseline predictors for hormonal treatment discontinuation. Use of analgesics (HR, 1.22; 95% CI, 1.08 to 1.37), hypnotics/sedatives (HR, 1.21; 95% CI, 1.07 to 1.37), antidepressants (HR, 1.22; 95% CI, 1.06 to 1.40), or GI drugs (HR, 1.27; 95% CI, 1.13 to 1.43), and switching therapy between tamoxifen and aromatase inhibitors (HR, 1.50; 95% CI, 1.23 to 1.83) during the first year of hormonal treatment were associated with increased risk of discontinuation during the next 4 years. Conclusion Predictors identified in our study can be used in developing targeted intervention to prevent adjuvant hormone therapy discontinuation and subsequently to improve breast cancer outcomes.