To examine trends and contributing factors of opioid, heroin, and cannabis-associated emergency department (ED) visits in Nevada.The 2009 to 2017 Nevada State ED database (n = 7,950,554 ED visits) were used. Use of opioid, heroin, and cannabis, respectively, was identified by the International Classification of Diseases, 9th & 10th Revisions. Three multivariable models, one for each of the 3 dependent variables, were conducted. Independent variables included year, insurance status, race/ethnicity, use of other substance, and mental health conditions.The number of individuals with opioid, heroin, cannabis-associated ED visits increased 3%, 10%, and 23% annually from 2009 to 2015, particularly among 21 to 29 age group, females, and African Americans. Use of other substance (odds ratio [OR] = 3.91; 95% confidence interval [CI] = 3.84, 3.99; reference - no use of other substance), mental health conditions (OR = 2.48; 95% CI = 2.43, 2.53; reference - without mental health conditions), Medicaid (OR = 1.41; 95% CI = 1.38, 1.44; reference - non-Medicaid), Medicare (OR = 1.44; 95% CI = 1.39, 1.49; reference - non-Medicare) and uninsured patients (OR = 1.52; 95% CI = 1.49, 1.56; reference - insured) were predictors of all three substance-associated ED visits.With a steady increase in trends of opioid, heroin, and cannabis-associated ED visits in recent years, the main contributing factors include patient sociodemographic factors, mental health conditions, and use of other substances.