Abstract Aims Myocardial work (MyW) is an echocardiographically derived parameter to estimate myocardial performance. The calculation of MyW utilizes pressure strain loops from global longitudinal strain and brachial blood pressure (BP) as a surrogate of left ventricular systolic pressure (LVSP). Since LVSP cannot be equated with BP in hypertrophic obstructive cardiomyopathy (HOCM), we explored whether LVSP can be derived non-invasively by combining Doppler gradients and BP. Methods and results We studied 20 consecutive patients (8 women, 12 men; mean age 57.0 ± 13.9 years; NYHA 2.1 ± 0.8; maximal septal thickness 24.7 ± 6.3 mm) with indication for first alcohol septal ablation. All measurements were performed simultaneously in the catheterization laboratory (CathLab)—invasively: ascending aortic and LV pressures; non-invasively: BP, maximal (CWmax) and mean (CWmean) Doppler gradients. LVSP was 188.9 ± 38.5 mmHg. Mean gradients of both methods were comparable (CathLab 34.3 ± 13.4 mmHg vs. CW 31.0 ± 13.7 mmHg). Maximal gradient was higher in echocardiography (64.5 ± 28.8 mmHg) compared with CathLab (54.8 ± 24.0 mmHg; P < 0.05). Adding BP (143.1 ± 20.6 mmHg) to CWmax resulted in higher (207.7 ± 38.0 mmHg; P < 0.001), whereas adding BP to CWmean in lower (174.1 ± 26.1 mmHg; P < 0.01) derived LVSP compared with measured LVSP. However, adding BP to averaged CWmax and CWmean resulted in comparable results for measured and derived LVSP (190.9 ± 31.6 mmHg) yielding a favourable correlation (r = 0.87, P < 0.001) and a good level of agreement in the Bland–Altman plot. Conclusion Non-invasive estimation of LVSP in HOCM is feasible by combining conventional BP and averaged CWmean and CWmax gradients. Hereby, a more reliable estimation of MyW in HOCM may be feasible.