OBJECTIVES: To investigate the relationship between excessive endogenous production of nitric oxide (NO) and the low systemic vascular resistance (SVR) syndrome after cardiac surgery. DESIGN: Prospective, case-control. Cases defined by low SVR postoperatively (< 750 dyn/s/cm-5), and matched with controls (> 900 dyn/s/cm-5). SETTING: Cardiothoracic intensive care unit (ICU) in a tertiary care hospital. PARTICIPANTS: Forty-four patients after cardiac surgery. INTERVENTIONS: Collection of plasma and urine samples after identification. MEASUREMENTS AND MAIN RESULTS: Plasma and urine nitrate concentrations were measured as an index of endogenous NO production. Hemodynamic, inotropic, and outcome data were collected. Median nitrate concentrations did not differ between cases and controls (plasma, 58 mumol/L, v 62 mumol/L, p = 0.43; urine, 399 mumol/L v 404 mumol/L, p = 0.38). Times to extubation and intensive care unit (ICU) discharge were prolonged in patients with low SVR (17.8 hours v 8.7 hours, p = 0.021; 2.5 days v 1.2 days, p = 0.019, respectively). CONCLUSIONS: No association between "low SVR syndrome" and endogenous NO production was found. Patients with low SVR after cardiac surgery required a longer period of inotropic and ventilator support, with delay in discharge from the ICU. The risk and cost implications of this syndrome support further research.