This study aimed to measure the frequency and severity of avoidable adverse events (AAEs) related to ignoring do-not-do recommendations (DNDs) in primary care. A retrospective cohort study analyzing the frequency and severity of AAEs related to ignoring DNDs (7 from family medicine and 3 from pediatrics) was conducted in Spain. Data were randomly extracted from computerized electronic medical records by a total of 20 general practitioners and 5 pediatricians acting as reviewers; data between February 2018 and September 2019 were analyzed. A total of 2557 records of adult and pediatric patients were reviewed. There were 1859 (72.7%) of 2557 (95% confidence interval CI, 71.0%-74.4%) DNDs actions in 1307 patients (1507 were performed by general practitioners and 352 by pediatricians). Do-not-do recommendations were ignored more often in female patients (P < 0.0001). Sixty-nine AAEs were linked to ignoring DNDs (69/1307 5.3%; 95% CI, 4.1%-6.5%). Of those, 54 (5.1%) of 1062 were in adult patients (95% CI, 3.8%-6.4%) and 15 (6.1%) of 245 in pediatric patients (95% CI, 3.1%-9.1%). In adult patients, the majority of AAEs (51/901 5.7%; 95% CI, 4.2%-7.2%) occurred in patients 65 years or older. Most AAEs were characterized by temporary minor harm both in adult patients (28/54 51.9%; 95% CI, 38.5%-65.2%) and pediatric patients (15/15 100%). These findings provide a new perspective about the consequences of low-value practices for the patients and the health care systems. Ignoring DNDs could place patients at risk, and their safety might be unnecessarily compromised. NCT03482232.