Background: No study has examined the prevalence of tobacco, other substance use, and symptoms of anxiety and depression, and rates of comorbidities among the orthopaedic trauma population, despite the impact they have on recovery from surgery. This study aims to 1) describe the rates of symptoms and substance use; 2) compare rates of symptoms and substance use among smokers versus non-smokers; and 3) examine the relationship between symptoms and substance use with smoking status. Methods: A cross-sectional survey of orthopaedic trauma patients was conducted in two Australian public hospitals. Demographic characteristics, smoking status, alcohol consumption, recent cannabis use, and symptoms of anxiety and/or depression were examined. Differences between current and non-smokers were compared using Pearson Chi 2 tests. Multivariate logistic regression explored variables related to tobacco smoking. Results: Eight hundred nineteen patients participated. Over one-fifth (21.8%) identified as a current smoker, half (51.8%) reported consuming alcohol at hazardous levels in the last 12 months, and about 10% stated that they had used cannabis in the last 30 days (9.7%), or experienced symptoms of either anxiety (12.4%), or depression (12.9%) in the last two weeks. Over one-fifth of current tobacco smokers (21.8%) reported drinking heavily in the last 12 months and using cannabis recently. Males, with a lower educational attainment, who were unmarried, had used cannabis recently, and report drinking heavily were more likely to be current smokers. Conclusions: Health behaviour interventions addressing comorbidities are warranted among the orthopaedic trauma population given the high rate of comorbidity and impact these may have on recovery.