Introduction: Although differential outcomes based on sex are widespread in medicine and surgery, evaluation of sex-specific differences in the field of orthopaedic surgery in general – and arthroplasty in particular – are lacking. We hypothesised that morbidly obese male and female patients would have differing risks of surgical complications following primary total hip replacement. Methods: We reviewed data contained within the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database from 2015 through 2018, inclusive. A multivariable binary logistic regression model was used to determine the adjusted odds ratios (OR) of relevant variables on primary and secondary outcomes. Results: A total of 86,684 patients undergoing THR were identified, of whom 9972 patients (4095 male and 5877 female) were morbidly obese. Among morbidly obese patients, odds of surgical site infection were higher in females than males within 30 days of surgery (adjusted OR 1.40; 95% CI, 1.10–1.79; p = 0.007). This comprised the odds of both superficial infection (1.8% vs. 1.1%, adjusted OR 1.67; 95% CI, 1.16–2.40; p = 0.006) and deep infection (1.9% vs. 1.4%, adjusted OR 1.22; 95% CI, 0.88–1.68; p = 0.24). Unexpected return to the operating room (i.e., reoperation) within 30 days of the surgical procedure was also higher among females than males (4.2% vs. 3.1%, adjusted OR 1.38, 95% CI, 1.10–1.71, p = 0.005). There were no differences between male and female patients in the non-obese cohort. Conclusions: Among patients with morbid obesity, the risk of surgical site infection and reoperation within the first 30 days is greater in women as compared to men. Future research must address whether this early increased risk among morbidly obese women persists in the longer term, and whether it results in compromised function or quality of life.