Abstract Purpose: Premenopausal women diagnosed with estrogen receptor (ER)-positive breast cancer are prescribed 5–10 years of endocrine therapy to prevent or delay recurrence. In this study, we evaluated the association between early discontinuation of endocrine therapy and breast cancer recurrence in a cohort of premenopausal women. Experimental Design: We identified 4,503 patients with premenopausal ER-positive breast cancer who initiated adjuvant endocrine therapy and were registered in the Danish Breast Cancer Group clinical database (2002–2011). Women were excluded if they had a recurrence or were lost to follow-up less than 1.5 years after breast cancer surgery. Endocrine therapy was considered complete if the patient received at least 4.5 years of treatment or discontinued medication less than 6 months before recurrence. Exposure status was updated annually and modeled as a time-dependent variable. We accounted for baseline and time-varying confounders via time-varying weights, which we calculated from multivariable logistic regression models, and included in regression models to estimate HRs and 95% confidence intervals (CIs) associating early discontinuation with recurrence. Results: Over the study follow-up, 1,001 (22%) women discontinued endocrine therapy. We observed 202 (20%) recurrences among those who discontinued endocrine therapy, and 388 (11%) among those who completed the recommended treatment. The multivariable-adjusted estimated rate of recurrence was higher in women who discontinued endocrine therapy relative to those who completed their treatment (hazard ratio, 1.67; 95% CI, 1.25–2.14). Conclusions: These results highlight the importance of clinical follow-up and behavioral interventions that support persistence of adjuvant endocrine therapy to prevent breast cancer recurrence.