INTRODUCTION: Cardiopulmonary stress test (CPT) plays important role in management of adult congenital heart disease (ACHD). Our aim in the current study is to investigate the role of a novel CPT parameter, O2-pulse-Heart rate inclination angle difference (IAD), that integrates chronotropic and inotropic responses to exercise, in the assessment of ACHD. METHODS: ACHD patients and healthy controls were enrolled prospectively for this observational study. Participants underwent transthoracic echocardiography and CPT on a bicycle ergometer with a ramp protocol, respectively. IAD was calculated in addition to standard CPT parameters in each patient. RESULTS: Twenty-one patients with ACHD (mean age: 28 ± 12 years, 14 male, 66 %) and 79 healthy controls (mean age: 34 ± 6, male 100 %) were included in the study. Patients had significantly lower systemic ventricle ejection fraction (60±8% versus 69±4%, p <.001) and higher systolic pulmonary artery pressure (33±13 versus 21±5 mmHg, p<.001). Execise duration (7.4±4 versus 10.1±2.3 minutes, p=.007), maximal oxygen consumption (VO2max) (1524±614 versus 2398±391, p<.001) and IAD (-5.9±13.7 versus 1.2±13.1°) were lower while VE/VCO2 was higher (31±5.1 versus 28.8±3.3,p=.030) in ACHD patients. In univariate analysis, age (r=0.236,p=.18), diagnosis of ACHD (r=-0.205,p=.41), NT-proBNP (r=-0.870,p=.002), VO2max (r=0.334,p=.001) and VE/VCO2 (r=-0.273, p=.006) were associated with IAD. IAD was independently associated with VE/VCO2 when adjusted by age, diagnosis of ACHD, LVEF and VO2max (β=-1.2, CI -1.892--0.508, R2=0.242) DISCUSSION AND CONCLUSION: In this study, we demonstrated that the novel CPT parameter IAD might have a potential role in assessing cardiovascular function in patients with ACHD. This role should be further investigated in larger cohorts.