To analyse the variation in the rate of AEs between acute hospitals and explore the extent to which some patients and hospital characteristics influence the differences in the rates of AEs. Methods - Retrospective cohort study. Binary logistic regression models were used to identify the potential association of some patients and hospital characteristics with AEs. A random sample of 4,250 charts, representative of around 180,000 hospital admissions, from 9 acute Portuguese public hospital centres in 2013, was analysed. Results – Main results: (i) AE incidence was 12.5%; (ii) 66.4% of all AEs were related to HAI and surgical procedures; (iii) patient characteristics such as sex, age, admission coded as elective vs urgent and medical vs surgical DRG code, all with p < 0.001, were associated with a greater occurrence of AEs – CCI seems to influence the difference in the rates of AEs; (iv) hospital characteristics such as use of reporting system, being accredited, university status and hospital size, all with p < 0.001, seem to be associated with a higher rate of AEs. We identified some patient and hospital characteristics that might influence the rate of AEs. Based on these results, more adequate solutions to improve patient safety can be defined.