Objectives. To examine prescription opioid and nonopioid analgesic use among US construction workers and their associations with pain conditions and sociodemographic factors. Methods. We analyzed data for about 9000 (weighted 11.5 million per year) construction workers who responded to the Medical Expenditure Panel Survey from 2011 to 2018. We applied both descriptive statistics and multiple logistic regression procedures in the analyses. Results. An estimated 1.2 million (10.0%) of construction workers used prescription opioid analgesics annually. The adjusted odds of prescription opioid use were significantly higher for workers suffering from work-related injuries (adjusted odds ratio [AOR] = 3.82; 95% confidence interval [CI] = 2.72, 5.37), non‒work-related injuries (AOR = 3.37; 95% CI = 2.54, 4.46), and musculoskeletal disorders (AOR = 2.31; 95% CI = 1.80, 2.95) after we controlled for potential confounders. Adjusted odds of prescription opioid use were also higher among workers with poorer physical health (AOR = 1.95; 95% CI = 1.42, 2.69) or mental health disorders (AOR = 1.95; 95% CI = 1.41, 2.68). Conclusions. Work- and non‒work-related injuries and musculoskeletal disorders significantly increased prescription opioid use among construction workers. To prevent opioid use disorders, multipronged strategies should be approached. (Am J Public Health. 2022;112(S1):S77-S87. https://doi.org/10.2105/AJPH.2021.306510).