Introduction: Frailty is a clinically recognizable state of decreased reserve and function across physiologic systems, characterized by an inability to cope with acute stressors. A validated modified frailty index (mFI) was used to evaluate the impact of frailty on postoperative complications following pancreaticoduodenectomy. Methods: Data from consecutive patients undergoing pancreaticoduodenectomy from 2011 to 2020 were collected retrospectively at a high-volume tertiary care hepatopancreatobiliary hospital. Based on an 11-item mFI, patients were grouped by high (≥0.27) and low mFI. The main outcome was postoperative complications (Clavien-Dindo classification). The impact of frailty on complications was analyzed by evaluating baseline and operative characteristics using multivariable logistic regression. Secondary outcomes included postoperative mortality, length of hospital stay, and intensive care unit (ICU) admission, which were analyzed using univariable logistic regression. Results: There were 64/554 patients (12%) with high mFI. Low and high mFI had similar characteristics, including proportion of pancreatic adenocarcinoma (low mFI = 247/490 [50%] vs. high mFI = 31/64 [48%], p = 0.767), intermediate or hard pancreatic texture (low mFI = 75/191 [39%] vs. high mFI = 6/19 [32%], p = 0.512), operative room time (low mFI = 370 min vs. high mFI = 368 min, p = 0.630), and drain placement (low mFI = 355/490 [72%] vs. high mFI = 48/64 [75%], p = 0.642). The mFI score was an independent predictor for the development of any type of postoperative complications (OR 1.44, 95% CI 1.02–2.10) and major postoperative complications (OR 1.44, 95% CI 1.05–1.98) by multivariable analysis. High mFI patients had a higher 90-day mortality rate (high mFI = 7/64 [11%] vs. low mFI = 20/490 [4.1%], p = 0.017), a longer median length of hospital stay (high mFI = 11 days vs. low mFI = 8 days, p = 0.016), and a higher rate of ICU admission (high mFI = 47/64 [73%] vs. low mFI = 211/490 [43%], p < 0.001). Conclusion: Among patients who are considered surgical candidates, the mFI can identify those at high risk of developing postoperative complications. This tool can be used to accurately discuss postoperative risk with patients undergoing pancreaticoduodenectomy.

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