Introduction: Increased prescribing of high potency opioids has been associated with increasing opioid addiction and linked to serious adverse outcomes including misuse, diversion, overdose and death. Problems related to opioids are a major Canadian public health concern yet few data are available on prescribing in most Canadian provinces. The objective of this study was to describe opioid prescribing in Ontario EDs and patient harms associated with this practice. Methods: We conducted a population-based cohort study among Ontario residents aged 15-64 years who were eligible for public drug coverage between April 2008 and March 2012. Using administrative databases, we identified patients with no opioid use in the past 12 months who received a prescription opioid from an emergency or family physician. Patients were followed for 2 years following their index prescription. The primary outcome was hospital admission for opioid toxicity and secondary outcome was dose-escalation exceeding 200 mg morphine equivalents (MEQ). Results: Of the 77,270 unique patients included, 33,492 (43.3%) and 43,778 (56.7%) prescriptions were issued by emergency physician (EP) and family physicians (FP), respectively. FP patients were older (45.9 vs 41.2 yr, MSD 0.35), had fewer ED visits (0.9 vs 2.3, MSD 0.46), and more FP visits (11.5 vs 8.7 MSD 0.31) in the year prior to their index visit. For combination products, EPs were more likely to prescribe oxycodone compared to FPs (37.2% vs 16.7%, Δ 20.5, 95% CI: 19.9, 21.2). For single agent products, EPs were more likely to prescribe hydromorphone compared to FPs (44.5% vs 21.7%, Δ 22.8, 95% CI: 20.4, 25.2). FPs were more likely to prescribe codeine either as a combination or single agent formulation. EP prescriptions led to significantly more hospital admissions for opioid toxicity (0.5% vs 0.3%, Δ 0.2, 95% CI: 0.1, 0.3), while FP prescriptions more often resulted in dose escalation beyond 200 mg MEQs (0.1% vs 0.7%, Δ 0.6, 95% CI: 0.4, 0.7). Conclusion: A large percentage of opioid-naïve patients receive an initial opiate prescription in the ED, where the use of high potency opioids is much more common, with 1/200 of these patients subsequently hospitalized for opioid toxicity. Creation of a physician accessible provincial registry would be useful to monitor opioid prescribing and dispensing, inform clinical practice, and identify patients at high-risk who may benefit from early interventions.