Abstract Background Globally, the clinical understanding of prostatitis has been obscured mainly due non-specificity of clinical features, no uniform diagnostic criteria and its protracted treatment course. Conventional treatment of chronic prostatitis by oral or parenteral routes of drug administration remains a challenge basically because of the poor ability of drugs to penetrate prostate epithelium; the alternative of direct prostate injection has not been thoroughly studied in an African population. The aim of this retrospective study was to determine the effect of transrectal ultrasound (TRUS)-guided intraprostatic injection of a cocktail of antibiotics, antifungal and long-acting steroids on alleviating symptoms attributed to chronic prostatitis in Ugandan patients. Methods We conducted a retrospective review of records among patients who were referred with symptoms attributed to chronic prostatitis at the Radiology Department of Ernest Cook Ultrasound Research and Education Institute (ECUREI). Patients were treated using TRUS-guided intraprostatic injection of a cocktail of antibiotics, antifungal agents and long-acting steroids. Results At baseline, we found that out of the 131 patients, 90 had pain or burning during urination in the last week to seeking care and 89 had symptoms, which had kept them away from doing the kinds of things they would usually do. Additionally, 85 of the total number of patients felt terrible about their symptoms. Post intervention, after 1 year following completion of intraprostatic injection therapy (IPIT), we found that most patients had mild residual symptoms which were largely; mild pain and burning at urination. None of the patients had symptoms, which kept them away from doing the kind of things they would usually do. Furthermore, 62 patients felt delighted about their quality of life, whereas prior to treatment, none was delighted. Eighty-five patients had felt terrible about their quality of life prior to the IPIT, but post therapy, no patient felt terrible. Conclusion Transrectal ultrasound-guided intraprostatic injection therapy of a drug cocktail composed of antibiotics, antifungal agents, long-acting steroids and lidocaine for treatment of patients presenting with symptoms attributed to chronic prostatitis and refractory to conventional oral therapy has shown a good response in this study.