Background: Transitional care may have different effects in males and females hospitalized for heart failure. We assessed the sex-specific effects of a transitional care model on clinical outcomes following hospitalization for heart failure. Methods: In this stepped-wedge cluster randomized trial of adults hospitalized for heart failure in Ontario, Canada, 10 hospitals were randomized to a group of transitional care services or usual care. Outcomes in this exploratory analysis were composite all-cause readmission, emergency department visit, or death at 6 months; and composite all-cause readmission or emergency department visit at 6 months. Models were adjusted for stepped-wedge design and patient age. Results: Among 2494 adults, mean (SD) age was 77.7 (12.1) years, and 1258 (50.4%) were female. The first composite outcome occurred in 371 (66.3%) versus 433 (64.1%) males (hazard ratio [HR], 1.04 [95% CI, 0.86–1.26]; P =0.67) and in 326 (59.9%) versus 463 (64.8%) females (HR, 0.83 [95% CI, 0.69–1.01]; P =0.06) in the intervention and usual care groups, respectively ( P =0.012 for sex interaction). The second composite outcome occurred in 357 (63.8%) versus 417 (61.7%) males (HR, 1.03 [95% CI, 0.85–1.24]; P =0.76) and 314 (57.7%) versus 450 (63.0%) females (HR, 0.81 [95% CI, 0.67–0.99]; P =0.037) in the intervention and usual care groups, respectively ( P =0.024 for sex interaction). The sex differences were driven by a reduction in all-cause emergency department visits among females (HR, 0.66 [95% CI, 0.51–0.87]; P =0.003), but not males (HR, 1.10 [95% CI, 0.85–1.43]; P =0.46), receiving the intervention ( P <0.001 for sex interaction). Conclusions: A transitional care model offered a reduction in all-cause emergency department visits among females but not males following hospitalization for heart failure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02112227.