Objectives: To investigate the efficacy and safety of perioperative administration of nitric oxide in cardiac surgery. Design: Meta-analysis of randomized controlled trials (RCTs). Participants: Cardiac surgery patients. Interventions: A search of Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE for RCTs that compared nitric oxide with placebo or other comparators. Measurements and Main Results: The primary outcome was intensive care unit (ICU) stay, and secondary outcomes were mortality, duration of mechanical ventilation, and reduction of mean pulmonary artery pressure. The study included 18 RCTs comprising 958 patients. The authors calculated the pooled odds ratio (OR) and the mean difference (MD) with random-effects model. Quantitative synthesis of data demonstrated a clinically negligible reduction in the length of ICU stay (MD –0.38 days, confidence interval CI [–0.65 to –0.11]; p = 0.005) and mechanical ventilation duration (MD –4.81 hours, CI [–7.79 to –1.83] ; p = 0.002) compared with all control interventions with no benefit on mortality. Conclusions: Perioperative delivery of inhaled nitric oxide resulted to be of no or minimal benefit in patients with pulmonary hypertension undergoing cardiac surgery. Large, randomized trials are needed to further assess its effect on major clinical outcomes and its cost-effectiveness. © 2018 Elsevier Inc.