ImportanceFrailty is associated with mortality following surgery and cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest. Despite the growing focus on frailty as a basis for preoperative risk stratification and concern that CPR in patients with frailty may border on futility, the association between frailty and outcomes following perioperative CPR is unknown.ObjectiveTo determine the association between frailty and outcomes following perioperative CPR.Design, Setting, and ParticipantsThis longitudinal cohort study of patients used the American College of Surgeons National Surgical Quality Improvement Program, including more than 700 participating hospitals in the US, from January 1, 2015, through December 31, 2020. Follow-up duration was 30 days. Patients 50 years or older undergoing noncardiac surgery who received CPR on postoperative day 0 were included; patients were excluded if data required to determine frailty, establish outcome, or perform multivariable analyses were missing. Data were analyzed from September 1, 2022, through January 30, 2023.ExposuresFrailty defined as Risk Analysis Index (RAI) of 40 or greater vs less than 40.Outcomes and MeasuresThirty-day mortality and nonhome discharge.ResultsAmong the 3149 patients included in the analysis, the median age was 71 (IQR, 63-79) years, 1709 (55.9%) were men, and 2117 (69.2%) were White. Mean (SD) RAI was 37.73 (6.18), and 792 patients (25.9%) had an RAI of 40 or greater, of whom 534 (67.4%) died within 30 days of surgery. Multivariable logistic regression adjusting for race, American Society of Anesthesiologists physical status, sepsis, and emergency surgery demonstrated a positive association between frailty and mortality (adjusted odds ratio [AOR], 1.35 [95% CI, 1.11-1.65]; P = .003). Spline regression analysis demonstrated steadily increasing probability of mortality and nonhome discharge with increasing RAI above 37 and 36, respectively. Association between frailty and mortality following CPR varied by procedure urgency (AOR for nonemergent procedures, 1.55 [95% CI, 1.23-1.97]; AOR for emergent procedures, 0.97 [95% CI, 0.68-1.37]; P = .03 for interaction). An RAI of 40 or greater was associated with increased odds of nonhome discharge compared with an RAI of less than 40 (AOR, 1.85 [95% CI, 1.31-2.62]; P < .001).Conclusions and RelevanceThe findings of this cohort study suggest that although roughly 1 in 3 patients with an RAI of 40 or greater survived at least 30 days following perioperative CPR, higher frailty burden was associated with increased mortality and greater risk of nonhome discharge among survivors. Identifying patients who are undergoing surgery and have frailty may inform primary prevention strategies, guide shared decision-making regarding perioperative CPR, and promote goal-concordant surgical care.