PURPOSE: To evaluate the clinical response and hemodynamic changes in the cavernosal arteries to combined therapy with trimix injection and sildenafil citrate in men with severe erectile dysfunction. PATIENTS AND METHODS: In all 40 patients were evaluated. Mean age 50.7 + 11.3 years. Fifteen patients (37.5%) with moderate ED and 25 (62.5%) with severe ED. Patients received 25 mg sildenafil once daily for 8 weeks and ICI with 0.25 mL trimix twice weekly. The penile hemodynamics were evaluated with Color Doppler ultrasound (CDUS) done at the begging and repeated after 8 weeks. Erection Hardness Score and satisfaction with treatment (EDITS) were assessed. RESULTS: Pretreatment hemodynamic parameters revealed normal response in five (12.5%), arterial insufficiency in five (12.5%), Veno-occlusive dysfunction in 26 (65%) and mixed arterial and VOD in 4 cases (10%). Improvement was found in 28 patients (70%); their mean age was 46.1 + 8.9 and range from 35 to 65 years. Adverse effects reported in 17 patients (42.5%). Responders revealed significant improvement in hemodynamic parameters, SHIM-5 score, time to and duration of erection and EHS. Comparison between responders and non-responders revealed significant difference regarding age, duration of ED, pre and post-treatment SHIM-5 score, time to and duration of erection, EHS with therapy and mean and standardized EDITS. CONCLUSION: The combination of ICI with triple agents plus oral PDE-5 inhibitor is an effective therapy in the patients with severe ED who do not respond to PDE-5 inhibitors or ICI of PGE1 monotherapy. Key