Abstract Background Heart failure (HF) is an increasing health problem globally. Current guidelines are based on studies with primarily male patients. Females are less likely to receive target dose of HF medication as recommended by the clinical guidelines. The reason for this is uncertain, but it has led to the question whether females might not need as high dosages as the males to achieve the beneficial effects of the HF medication. Aim To assess baseline predictors for achieving optimal medical treatment (OMT) and the prognostic importance of OMT for male and female patients who have attended a HF clinical program (HFCP). Methods OPTIHEART included 870 patients with left ventricular ejection fraction (LVEF) <45% leaving HFCP in 2018, 2019 or 2020 and followed in registers for a mean of 1083(SD 11.3) days. OMT was defined as receiving an angiotensin-converting-enzyme-inhibitor (ACEi), angiotensin-receptor blocker (ARB) or angiotensin-II-receptor blocker and nephrylisin-inhibitor (ARNI) AND a betablocker both in doses > 50% of target dose. Association between baseline data at referral and OMT at end of HFCP were calculated using logistic regression. The association between OMT and a 5-point Major Adverse Cardiovascular Event (a 5-Point MACE consisting of cardiovascular mortality, non-fatal acute myocardial infarction, non-fatal stroke, coronary revascularization, worsening of heart failure (both hospitalisation and re-referral to HFC)), were calculated and adjusted for other cardiovascular risk factors using multiple Cox-regression analyses. Results Achieving OMT was associated with male sex (OR: 2.05 95%CI 1.44-2.97; P<0.0001) independently of younger age, higher diastolic blood pressure (DBP), and lower creatinine at referral. A lower rate of 5-point MACE was associated achieved OMT (HR: 0.67 95%CI 0.50-0.89; P=0.006) independently of female sex (HR: 0.62 95%CI 0.47-0.82; P=0.002), younger age, never smoking and NYHA≤2. The beneficial effect of OMT was more pronounced in patients with BMI<26.5kg/m2 (HR=0.41[0.23-0.72] vs. HR=0.84[0.58-1.21], Pinteraction= 0.02), and insignificantly more pronounced in patients with male sex, older age, higher creatinine, and lower DBP. Conclusion OMT was more frequently achieved in patients with male sex independently of lower age, higher DBP, and lower creatinine. Achieving OMT was associated with less 5-point MACE independently of female sex, younger age, never smoking and NYHA≤2 and especially in patients with BMI<26.5kg/m2.Hazard RatioMedical treatment