This study aimed to evaluate the effectiveness of ICI of platelet-rich plasma (PRP) in addition to daily oral tadalafil intake in diabetic erectile dysfunction (ED) patients non-responding to PDE5 inhibitors. Overall, 48 patients complaining of ED non-responding to on-demand PDE5 inhibitors were allocated into 2equal groups, diabetics and non-diabetics that were given a daily dose of 5mg tadalafil plus vardenafil 20mg on demand during the study besides being subjected to 3 doses of ICI of PRP, 4weeks apart. Responses to on-demand PDE5 inhibitors, International index of erectile function-5 (IIEF-5) score, erection hardness scores (EHS) and pharmaco-dynamic duplex studies were assessed. After PRP injections, 33% and 50% of cases were satisfied with on-demand PDE5 inhibitors, respectively, whereas 41% and 66% of them showed improved EHS response. Compared with baseline scores, the mean IIEF-5scores were significantly improved after PRP therapy in the diabetic ED group (12.1 vs. 8.04, p=0.003) as well as in the non-diabetic ED group (14.8 vs. 10.2, p=0.001) linked to pharmaco-penile duplex readings. Both good and fair diabetic control exhibited significant responses to ICI therapy of PRP compared with bad controlled cases. The significant improvement included; the IIEF-5score increase (86.7%, 126% vs. 16.1%), improved EHS as well as penile duplex readings. Baseline HbA1C demonstrated a significant negative correlation with IIEF-5score before (p=0.019) and after PRP therapy (p=0.002) respectively. It could be concluded that ICI of PRP could be an effective therapy for treating ED patients non-responding to on-demand oral PDE5 treatment.