Background Obesity-based cutoffs in TKA are premised on higher rates of postoperative complications. However, operative time may be associated with postoperative complications, leading to an unnecessary restriction of TKA in patients with obesity. If operative time is associated with these obesity-related outcomes, it should be accounted for in order to ensure all measurable factors associated with negative outcomes are examined for patients with obesity after TKA. Questions/purposes We asked: (1) Is operative time, controlling for BMI class, associated with readmission, reoperation, and postoperative major and minor complications? (2) Is operative time associated with a difference in the direction or strength of obesity-related adverse outcomes? Methods In this comparative study, we extracted all records on elective, unilateral TKA between January 2014 and December 2020 in the American College of Surgeons National Surgical Quality Improvement Program database, resulting in an initial sample of 394,381 TKAs. Patients with emergency procedures (0.1% [270]) and simultaneous bilateral TKAs (2% [8736]), missing or null data (1% [4834]), and those with operative times less than 25 minutes (0.1% [548]) were excluded, leaving 96% (379,993) of our original sample size. The National Surgical Quality Improvement Program database was selected because of its inclusion of operative time, which is not found in any other national database. BMI was subdivided into underweight (BMI < 18.5 kg/m², < 1% [719]), normal weight (BMI 18.5 to 24.9 kg/m², 9% [34,513]), overweight (BMI 25.0 to 29.9 kg/m², 27% [101,538]), Class I obesity (BMI 30.0 to 34.9 kg/m², 29% [111,712]), Class II obesity (BMI 35.0 to 39.9 kg/m², 20% [76,605]), and Class III obesity (BMI ≥ 40.0 kg/m², 14% [54,906]). The mean operative time was 91 ± 36 minutes, 61% of patients were women (233,062 of 379,993), and the mean age was 67 ± 9 years. Patients with obesity tended to be younger and more likely to have preoperative comorbidities and longer operative times than patients with normal weight. Multivariable logistic regression models examined the main effects of operative time with respect to 30-day readmission, reoperation, and major and minor medical complications, while adjusting for BMI class and other covariates including age, sex, race, smoking status, and number of preoperative comorbidities. We then evaluated the potential interaction effect of BMI class and operative time. This interaction term helps determine whether the association of BMI with postoperative outcomes changes based on the duration of the surgery, and vice versa. If the interaction term is statistically significant, it implies the association of BMI with adverse postoperative outcomes is inconsistent across all patients. Instead, it varies with the operative time. Adjusted odds ratios and 95% confidence intervals were calculated, and interaction effects were plotted. Results After controlling for obesity, longer procedure duration was independently associated with higher odds of all outcomes (30-minute estimates; adjusted ORs are per minute), including readmission (9% per half-hour of surgical duration; adjusted OR 1.003 [95% CI 1.003 to 1.004]; p < 0.001), reoperation (15% per half-hour of surgical duration; adjusted OR 1.005 [95% CI 1.004 to 1.005]; p < 0.001), postoperative major complications (9% per half-hour of surgical duration; adjusted OR 1.003 [95% CI 1.003 to 1.004]; p < 0.001), and postoperative minor complications (18% per half-hour of surgical duration; adjusted OR 1.006 [95% CI 1.006 to 1.007]; p < 0.001). The interaction effect indicates that patients with obesity had lower odds of reoperation than patients with normal weight when operative times were shorter, but higher odds of reoperation with a longer operative duration. Conclusion We found that operative time, a proxy for surgical complexity, had a moderate, differential association with obesity over a 30-minute period. Perioperative modification of surgical complexity such as surgical techniques, training, and team dynamics may make safe TKA possible for certain patients who might have otherwise been denied surgery. Decisions to refuse TKA to patients with obesity should be based on a holistic assessment of a patient's operative complexity, rather than strictly assessing a patient's weight or their ability to lose weight. Future studies should assess patient-specific characteristics that are associated with operative time, which can further push the development of techniques and strategies that reduce surgical complexity and improve TKA outcomes. Level of Evidence Level III, therapeutic study. [ABSTRACT FROM AUTHOR]