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ObjectiveTo investigate the effect of chronic use of sildenafil and intracavernous injection (ICI) with trimix in men not responding to on-demand monotherapy with sildenafil or ICI with prostaglandin-E1 (PGE1).Patients and methodsThe study included 40 patients with erectile dysfunction (ED), with a mean (SD) age of 50.7 (11.3) years and unresponsive to on-demand sildenafil or ICI with PGE1 as monotherapy. They were assessed using the Sexual Health in Men (SHIM)-5 score for ED severity, penile colour Doppler ultrasonography (CDUS) for peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) with an ICI test using 0.25 mL of trimix of papaverine, PGE1 and phentolamine. Testosterone, prolactin and cholesterol levels were assessed. Patients received 25 mg sildenafil daily for 8 weeks, combined with twice weekly ICI with 0.25 mL of trimix. After treatment, the Erection Hardness Score (EHS), penile CDUS with ICI and ED Inventory of Treatment Satisfaction were assessed.ResultsThe mean (SD) SHIM-5 score before treatment was 8.3 (0.5) in 15 of the 40 men and 6.3 (0.4) in 25. Penile haemodynamics were normal in five (13%), showed arterial insufficiency in five (13%), venous occlusive disease in 26 (65%) and mixed vascular in four (10%). There was an improved SHIM-5 score in 28 (70%) patients, as shown by their haemodynamic values, duration of erection and EHS with therapy, and 66% satisfaction with treatment. Adverse effects (penile pain, headache, facial flushing, dyspepsia, nasal congestion, dizziness) were reported in 17 patients (43%).ConclusionChronic use of trimix plus daily low-dose sildenafil improved penile haemodynamics in these patients with ED not responding to on-demand phosphodiesterase-5 inhibitors or ICI with PGE1 monotherapy.