Patients on antidepressant or antianxiety medications often have complex perioperative courses due to difficult pain management, altered coping mechanisms, or medication-related issues. This study examined the relationship between preoperative antidepressants and antianxiety medications on postoperative hospital length of stay while controlling for confounding variables. From an administrative database of 48,435 adult patients who underwent noncardiac surgery from 2011 to 2014 at a single, large urban academic institution, multivariable zero-truncated negative binomial regression analyses controlling for age, sex, medical comorbidities, and surgical type were performed to assess whether preoperative exposure to antidepressant or antianxiety medication use was associated with postoperative hospital length of stay. There were 5111 (10.5%) patients on antidepressants and 4912 (10.1%) patients on antianxiety medications. The median length of stay was 3 days (interquartile range = 2-6). After controlling for confounding variables, preoperative antidepressant medication was associated with increased length of stay with an incidence rate ratio of 1.04 (99% confidence interval, 1.0-1.08, P < .001) and antianxiety medication with an incidence rate ratio of 1.1 (99% confidence interval, 1.06-1.14; P < .001). The association between antidepressants or antianxiety medications and increased postoperative length of stay suggests that these patients may require greater attention in the perioperative period to hasten recovery, which may involve integrating preoperative counseling, postoperative psychiatric consults, or holistic recovery approaches into enhanced recovery protocols.