Introduction: Substance and opioid misuse are growing public health concerns in Canada. Substance use disorders affect 21.6% of Canadians and accounted for $267 million in healthcare costs in 2011. Opioid misuse is a current public health crisis. The extent of the rise in substance and opioid misuse-related Emergency Department (ED) visits in Canada and the demographic groups in which the rise is concentrated have not been elaborated. Alberta has one of the most complete provincial ED visit records and provides an important understanding of national trends. The objective of this study was to evaluate trends in substance and opioid misuse-related ED visits in Alberta from 2010/11 to 2014/5 within demographic cross-sections of the population using administrative ED visit data from the National Ambulatory Care Reporting System (NACRS). Methods: All visits made by adult patients (18 years old) to any of more than 100 Albertan EDs for a substance misuse-related presentation between 2010/11 and 2014/15 were analyzed. Visits were classified as being related to substance or opioid misuse if the primary and/or secondary visit diagnoses were among an a priori determined group of ICD-10 codes. Annual substance misuse-related visits were compared as visits per 100,000 adult population in Alberta to standardize for population growth. Linear regression was used to assess whether ED visits increased significantly over time. A cross-sectional time-series analysis was employed to examine trends within subgroups defined by sex and age categories (18-29, 30-39, 40-49, 50-59, and 60 years) over a 60-month period. Results: 149,719 substance misuse-related visits were made by 65,089 patients and 8768 opioid misuse-related visits were made by 5763 patients. From 2010/11 to 2014/15, substance misuse-related ED visits in Alberta increased by 38% from 811 to 1119 visits per 100,000 population. Opioid misuse-related ED visits increased significantly (64%) from 44 to 72 per 100,000 population. Conversely, total ED visits per 100,000 population did not increase significantly. Substance and opioid misuse-related visits rose more in non-rural than rural areas. Cross-sectional time-series analysis showed that the greatest increase in substance and opioid misuse-related ED visits occurred in males and in the 18-29 year age category, in which visit increases for opioid misuse appeared exponential. Conclusion: Substance and opioid misuse-related ED visits increased significantly from 2010/11 to 2014/15 in Alberta, with the most dramatic increases occurring in young patients and males. These findings have important implications for targeting urgent preventative public health interventions to stem the rise of this epidemic.