Background and Objectives Tobacco use and co‐prescription of sedative hypnotics are risk factors for misuse of prescribed opioids among patients with non‐cancer pain. However, the association between tobacco use and these co‐prescriptions has not been clarified. We aimed to assess differences in the prescription and co‐prescription rates of opioid analgesics with muscle relaxants and/or benzodiazepines between tobacco users and non‐users. Methods Visit data were obtained from the 2006 to 2009 National Ambulatory Medical Care Survey, an annual cross‐sectional survey of visits to office‐based physicians in outpatient settings in the United States. Our sample patients were aged ≥18 years and diagnosed with non‐cancer back and neck pain. The χ2 test and multiple logistic regression analysis were used to assess bivariate and multivariate associations between prescription or co‐prescription rates and tobacco use status. Results We analyzed a total of 114,199,536 weighted visits (unweighted number: 3,521). Significant odds ratios (ORs) of tobacco users (vs non‐users) for medical prescriptions were as follows: opioid analgesics, OR 2.14, 95% confidence interval (CI) 1.64–2.80; muscle relaxants and opioid analgesics, OR 2.57, 95%CI 1.76–3.74; benzodiazepines and opioid analgesics, OR 3.66, 95%CI 2.11–6.35, and muscle relaxants, benzodiazepines, and opioid analgesics, OR 7.02, 95%CI 2.98–16.57. Conclusions and Scientific Significance Tobacco users were more likely to receive prescriptions for opioid analgesics with muscle relaxants and/or benzodiazepines than non‐users. Healthcare professionals need to limit co‐prescription of opioid analgesics with muscle relaxants and/or benzodiazepines among tobacco users and provide a comprehensive approach to pain management. (Am J Addict 2019;XX:1–8)