Opioids poisoning is of the most important cause of mortality. The objective of the study was to compare the demographic factors, clinical manifestations, and outcomes of the most common opioids involved in drug overdose presenting to the Emergency Department. Methods: This cross-sectional study was conducted from October 2016 to March 2017 in the Clinical Toxicology Department of the main referral center of the university. All poisoning cases with common opioids were included in the study. Demographic factors, clinical manifestations, and outcome were recorded in a check list. ANOVA, Chi-square or Fisher's exact test, and binary logistic regression analysis were used for outcome prediction. Findings: Two hundred and thirty six patients with opioids poisoning were evaluated during the study period. The most common opioids involved in poisoning were methadone (47.9%), tramadol (24.2%), and opium (21.6%). Patients with opium poisoning were older than others (P < 0.0001). The rate of suicide was more in the tramadol group, while the past history of psychological problems was more observed in the methadone group (P < 0.0001). Increasing age (odds ratio [OR], 1.05; 95% confidence interval [CI]: 1.02–1.09; P = 0.05) and addiction (P = 0.01; OR, 7; 95% CI: 1.55–31.52) was associated with an increased complications or death. Also patients with somatic disease had more chance of complications/death (P = 0.04; OR, 3.71; 95% CI: 1.06–12.97). Kind of opioids was not a predictive factor in the outcome of the patients with acute poisoning. Conclusion: Age, addiction, and somatic disease should be considered as more important factors in outcome prediction with opioids poisoning, including opium, tramadol, and methadone.