This prospective study assessed the long-term effects of self-injection of papaverine hydrochloride and phentolamine mesylate along several critical domains for 42 men and 26 partners. Over the course of one year, men were, on average, injecting themselves five times monthly, with 84% of these injections producing satisfactory erections. Treatment resulted in statistically significant improvements in quality of erection, sexual satisfaction, frequency of intercourse, and coital orgasm. The women also demonstrated significant improvement in sexual satisfaction, arousal, frequency of intercourse, and coital orgasm. Decreases in general psychiatric symptomatology were apparent for men but not for partners. The dropout rate was 57%. The common side effects of treatment were development of fibrotic nodules (26%), abnormal liver function values (30%), and bruising (19%). We conclude that self-injection should be considered among the accepted treatments for erectile dysfunction. It does appear to enhance the sexual lives of men and women when the treatment is efficacious and the couple is motivated to utilize it.