Background Combined minimum apparent diffusion coefficient (ADC) and ADC difference value may improve the diagnostic performance of breast diffusion-weighted imaging (DWI) compared with mean ADC. Purpose To investigate whether ADC parameters at DWI are associated with distant metastasis-free survival in women with invasive breast cancer. Materials and Methods Between 2013 and 2014, 258 consecutive women (mean age ± standard deviation, 50.9 years ± 10.5; age range, 23-85 years) with newly diagnosed invasive breast cancer who underwent preoperative MRI with DWI were evaluated. All DWI examinations were retrospectively reviewed by two radiologists blinded to clinical information. The mean, minimum, and maximum ADCs were measured by manually placing regions of interest within the lesions, and the ADC difference value (the difference between minimum and maximum ADCs) was calculated to evaluate intratumoral heterogeneity. Cox proportional hazards models were used to determine the associations between ADC parameters and distant metastasis-free survival after adjustment for clinical-pathologic factors. Results In 25 of the 258 women (9.7%), distant metastasis developed at a median follow-up of 51 months. The ADC difference value was higher in women with distant metastasis than in those without distant metastasis (mean, 0.743 × 10-3 mm2/sec vs 0.566 × 10-3 mm2/sec, respectively; P < .001). Multivariable Cox proportional hazards analysis showed that a higher ADC difference value (>0.698 × 10-3 mm2/sec) (hazard ratio [HR], 4.5; 95% confidence interval [CI]: 2.0, 10.0; P < .001), presence of axillary node metastasis (HR, 3.3; 95% CI: 1.2, 9.3; P = .02), and estrogen receptor negativity (HR, 2.6; 95% CI: 1.2, 5.7; P = .02) were associated with poorer distant metastasis-free survival. Conclusion A higher apparent diffusion coefficient difference value at diffusion-weighted imaging is associated with poorer distant metastasis-free survival of women with invasive breast cancer. © RSNA, 2019 See also the editorial by Taourel in this issue.