Persistent postoperative pain (PPP) has been described as a complication of cardiac surgery (CS). We aimed to study PPP after CS (PPPCS) by conducting a systematic review of the literature regarding its incidence, intensity, location, and the presence of neuropathic pain, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The review comprised 3 phases: a methodological assessment of 6 different databases identifying potential articles and screening for inclusion criteria by 2 independent reviewers; data extraction; and study quality assessment. Meta-analysis was used to estimate the pooled incidence rates using a random effects model. We have identified 442 potentially relevant studies through database searching. A total of 23 studies (involving 11,057 patients) met our inclusion criteria. Persistent postoperative pain affects 37% patients in the first 6 months after CS, and it remains present more than 2 years after CS in 17%. The reported incidence of PPP during the first 6 months after CS increased in recent years. Globally, approximately half of the patients with PPPCS reported moderate to severe pain. Chest is the main location of PPPCS followed by the leg; neuropathic pain is present in the majority of the patients. This is the first systematic review and meta-analysis to provide estimates regarding incidence and intensity of PPPCS, which elucidates its relevance. There is an urgent need for adequate treatment and follow-up in patients with PPPCS.