Early pharmacological prophylaxis has been reported to increase the return of spontaneous erections following radical prostatectomy (RP). In this study, we evaluated the role of intracavernosal alprostadil (PGE1) combined with sildenafil in stimulating early recovery of spontaneous erections following RP. In this prospective study, we included 22 patients who underwent bilateral nerve-sparing RP after October 2004. Sildenafil dose of 50 mg/day was started at the time of hospital discharge. Of 22 patients, 18 started on PGE1-4 microg (1-8) and four started on low-dose Trimix (20 U) 2-3 times/week. These patients are followed up at regular intervals (3, 6, 9 and 12 months) with abridged version of the International Index for Erectile Function-5 questionnaire. Patient compliance, return of sexual activity and return of natural erection, adverse effects and reasons for discontinuation were recorded. Penile doppler studies were performed during followup visits to assess the vascular status. After a mean followup of 6 months (3-8 months), 11/22 (50%) patients had return of spontaneous partial erections. Of the 18 PGE1 users, six continued 4 microg PGE1, four increased the dose to 8 microg, six decreased the dose to 2 microg and two patients further reduced the dose to 1 microg. Of four low-dose Trimix users, three increased the dose to 30 U and one reduced the dose to 15 U. Of 22 patients, 21 were sexually active: 12/21 (57%) with the injections alone and 9/21 (42.9%) with combination therapy (injections (PGE1) and sildenafil). Penile doppler studies revealed arterial insufficiency in 77% (17/22) patients and venous insufficiency in one patient. Early intracavernosal injections following RP facilitated early sexual intercourse, patient satisfaction and potentially earlier return of natural erections. Early combination therapy with sildenafil allowed a lower dose of intracavernous injections, minimizing the penile discomfort.