ABSTRACT: Importance:Sex differences in postoperative outcomes in patients with heart failure (HF) have not been well characterized. Women generally experience a lower postoperative mortality risk after noncardiac operations. It is unclear if this pattern holds among patients with HF. Objectives:To determine if the risk of postoperative mortality is associated with sex among patients with HF who underwent noncardiac operations and to determine if sex is associated with the relationship between HF and postoperative mortality. Design, Setting, and Participants:This multisite cohort study used data from the US Department of Veterans Affairs Surgical Quality Improvement Project database for all patients who underwent elective noncardiac operations from October 1, 2009, to September 30, 2016, with a minimum of 1 year follow-up. The data analysis was conducted from May 1, 2018, to August 31, 2018. Exposures:Heart failure, left ventricular ejection fraction, and sex. Main Outcomes and Measures:Postoperative mortality at 90 days. Results:Among 609?735 patients who underwent elective noncardiac operations from 2009 to 2016, 47?997 patients had HF (7.9%; mean [SD] age, 68.6 [10.1] years; 1391 [2.9%] women) and 561?738 patients did not have HF (92.1%; mean [SD] age, 59.4 [13.4] years; 50?862 [9.1%] women). Among patients with HF, female sex was not independently associated with 90-day postoperative mortality (adjusted odds ratio [aOR], 0.97; 95% CI, 0.71-1.32). Although HF was associated with increased odds of postoperative mortality in both sexes compared with their peers without HF, the odds of postoperative mortality were higher among women with HF (aOR, 2.44; 95% CI, 1.73-3.45) than men with HF (aOR, 1.64; 95% CI, 1.54-1.74), suggesting that HF may negate the general protective association of female sex with postoperative mortality (P for interaction of HF?×?sex?=?.03). This pattern was consistent across all levels of left ventricular ejection fraction. Conclusions and Relevance:Although HF was associated with increased odds of postoperative mortality in both sexes compared with their peers without HF, the odds of postoperative mortality were higher among women with HF than men with HF, suggesting that HF may negate the general protective association of female sex with postoperative mortality risk in noncardiac operations.