BACKGROUND Cardiac surgery (CS) ranks among the most frequently performed interventions worldwide and persistent postoperative pain (PPP) has been recognized as a relevant clinical outcome in this context. We aimed to evaluate its incidence, characteristics, associated factors and patient's quality of life (QoL). METHODS Observational prospective study conducted in patients undergoing CS in a tertiary university hospital. PPP was defined as persistent pain after surgery with higher than 3 months' duration, after excluding other causes of pain. We used a set of questionnaires for data collection: Pain Catastrophizing Scale, Duke Health Profile, Brief Pain Inventory Short Form, McGill Pain Questionnaire Short Form, Douleur Neuropathique en 4 Questions and standardized questions regarding pain periodicity. RESULTS A total of 288 patients have completed the study and 43% presented PPP assessed at 3 months (PPP3M); out of which 84% were not under any treatment. PPP patients reported significantly lower QoL, and a neuropathic pain (NP) component was present in 50% of them. Younger age, female gender, higher body mass index, catastrophizing, coronary artery bypass graft, osteoarthritis, history of previous surgery (excluding sternotomy) and moderate to severe acute postoperative pain were independent predictors of PPP3M. CONCLUSION This is the first study comprehensively describing PPP after CS and identifying NP in half of them. Our results support the important role that PPP plays after CS in considering its interference in patients' daily life and their lower QoL, which deserves the attention of health care professionals in order to improve prevention, assessment and treatment of these patients. WHAT DOES THIS STUDY ADD?: This study comprehensively describes persistent postoperative pain (PPP) after cardiac surgery (CS) and identifies neuropathic pain (NP) in half of them. Our results support the important role that PPP plays after CS in considering its interference in patients' daily life and their lower quality of life.