Intracavernosal injection therapy (ICI) was the first pharmacologic treatment in the management of erectile dysfunction. ICI allows for customization of medication composition and concentrations, making it a highly effective treatment with an acceptable side effect profile. The objective was to investigate the long-term results of ICI using validated and non-validated instruments. This is a retrospective, single-institution study of 105 patients (mean age 61.6 ± 11.1) patients using ICI. Mean duration of ICI was 8.4 ± 6.25 years. Pre- and post-treatment patient-reported penile rigidity were 41.1% ± 29.3 and 89.6% ± 13.6, respectively (p < 0.05). Statistical changes were also found in the pre and post International Index of Erectile Function (IIEF) scores (33.0 ± 14.4 and 60.0 ± 12.7, p < 0.05), erectile function (11.5 ± 1.3 and 27.3 ± 0.9, p < 0.05) and satisfaction domains (5.3 ± 1.5 and 8.1 ± 1.1, p < 0.05) of the IIEF. There were no statistical differences in questionnaire outcomes between difficult to treat patients (diabetes or radical prostatectomy) and the remainder of queried patients. Complications were rare and included priapism (7.1%), penile curvature (10%; <30°), bruising (7.6%), and mild penile pain (12.4%). Overall, ICI therapy is safe and effective, and compliance may be augmented by patient education, dosing customization, and cost reduction.