Background: The association between marijuana use and surgical procedures is a matter of increasing societal relevance that has not been well studied in the literature. The primary aim of this study is to evaluate the relationship between marijuana use and in-hospital mortality, as well as to assess associated comorbidities in patients undergoing commonly billed orthopedic surgeries. Methods: The National Inpatient Sample (NIS) database from 2010 to 2014 was used to determine the odds ratios for the associations between marijuana use and in-hospital mortality, heart failure (HF), stroke, and cardiac disease (CD) in patients undergoing 5 common orthopedic procedures: total hip (THA), total knee (TKA), and total shoulder (TSA) arthroplasties, spinal fusion, and traumatic femur fracture fixation. Results: Of 9,561,963 patients who underwent one of the 5 selected procedures in the 4-year period, 26,416 (0.28%) were identified with a diagnosis of marijuana use disorder. In hip and knee arthroplasty patients, marijuana use was associated with decreased odds of mortality compared with no marijuana use (P <.0001) and increased odds of HF (P =.018), stroke (P =.0068), and CD (P =.0123). Traumatic femur fixation patients had the highest prevalence of marijuana use (0.70%), which was associated with decreased odds of mortality (P =.0483), HF (P =.0076), and CD (P =.0003). For spinal fusions, marijuana use was associated with increased odds of stroke (P <.0001) and CD (P <.0001). Marijuana use in patients undergoing total shoulder arthroplasty was associated with decreased odds of mortality (P <.001) and stroke (P <.001). Conclusions: In this study, marijuana use was associated with decreased mortality in patients undergoing THA, TKA, TSA, and traumatic femur fixation, although the significance of these findings remains unclear. More research is needed to provide insight into these associations in a growing surgical population.