Determine the frequency and preventability of adverse events (AEs) from available information sources in selected ambulatory care (AC) sites in Latin America (LA). Multinational observational cohort was conducted to determine the period prevalence (retrospective focus) and the cumulative incidence (prospective focus) of AEs. Outpatient clinics in Mexico, Peru, Brazil and Colombia. A random selection of 2080 patients. The existence of AE was decided based on trigger information provided by the patient and crossing the data with each patient's medical history. AE occurrences 6 months prior (prevalence) and 42 days after (incidence) the patient receiving AC were identified. AE type and preventability were also described. Two thousand eighty patients participated in the study. AEs prevalence was 5.2% (108/2080) [95% confidence interval (CI) 4.2–6.1%], and cumulative incidence was 2.4% (42/1757) (95% CI 1.7–3.1%). AEs considered preventable were 44% (55/108) of prevalence period, and 52.4% (22/42) of incidence period. Preventability was associated with patient socioeconomic status (OR 3.5, 95% CI 1.4–8.8), medication error (OR 0.1, 95% CI 0.0–0.4), diagnostic error (OR 0.1, 95% CI 0.0–0.8) and a minor impact on the patient (OR 0.2 95% CI 0.1–0.9). The frequency of AE in ambulatory settings in LA is in the high-frequency range of research focused on the prevalence of AEs. Fifty percent was preventable. This study provides an approach for assessing the frequency and preventability of AE in order to enhance patient safety in LA.