Purpose: We aimed to describe characteristics of new users of ticagrelor or clopidogrel following a recent coronary event, and to compare incidences of selected safety outcomes. Methods: This observational cohort study used data from national Swedish registers. Patients first dispensed ticagrelor or clopidogrel (June 2011–December 2013) were identified from the Prescribed Drug Register and followed until censoring or 31 December 2014. Cohorts were restricted to patients with a recent coronary event-related hospital contact identified in the Patient Register. Results: The study included 45 987 unique, naïve users of ticagrelor (73% men; mean age 66 years) or clopidogrel (69% men; mean age 69 years). Corresponding to indication, diagnoses before initiation were acute coronary syndrome (93%), myocardial infarction (76%), and percutaneous coronary intervention (69%). The most common medications used in the year before initiation of study therapy were antithrombotic agents (clopidogrel 62%, ticagrelor 43%), mainly low-dose acetylsalicylic acid. Ticagrelor users had a higher incidence (per 1000 person-years) of respiratory bleeding (24.6 [95% confidence interval (CI): 22.1–27.3]; vs clopidogrel users: 14.4 [13.1–15.8]) and dyspnea (25.9 [23.3–28.7]; vs clopidogrel users: 16.8 [15.4–18.4]). Epistaxis accounted for 83–93% of respiratory bleeds. Adjusted analyses found increased risks of gout and acute renal failure with ticagrelor. Conclusions: Clopidogrel users were older with a higher prevalence of concomitant medications than ticagrelor users. Our study showed increased incidences of dyspnea and respiratory bleeding (mainly epistaxis) among current ticagrelor users compared with clopidogrel users, and increased risks of gout and acute renal failure after adjustment.