Background: Hematospermia, although often found to be a benign condition, can be an alarming sign. Consequently, patients can undergo multiple investigations with no current standardized pathway based on data from large series. The aim of this study was to evaluate the incidence of an underlying pathology and the value of diagnostic investigations performed in patients presenting with hematospermia. Materials and methods: A retrospective review of 393 consecutive men who underwent investigations for hematospermia was performed in a single tertiary center. Patient demographics, radiological and microbiological results were recorded together with symptoms of concomitant hematuria and clinical outcomes. Results: In this cohort, the overall prostate cancer detection rate was 5.3% and 7.2% in the ≥40 years group. One patient was diagnosed with testicular seminoma detected on scrotal ultrasound scan and one with G1pTa urothelial carcinoma of the bladder detected on flexible cystoscopy. In addition, 5.6% of patients were found to have a significant benign pathology for which intervention was proposed. A total of 288 patients underwent a transrectal ultrasound scan and 58.7% (n = 169) of these patients were found to have a positive finding. One hundred ten patients underwent a multiparametric magnetic resonance imaging and 73.6% (n = 81) had a positive finding. Conclusions: Apart from transrectal ultrasound and multiparametric magnetic resonance imaging, the remaining investigations have a low diagnostic yield. Prostate cancer detection was 5.3%; 7.2% in the ≥40 years group, and two further patients were diagnosed with testicular and bladder malignancy. Based on our results, we propose an algorithm for the management of hematospermia to limit unnecessary investigations with the majority requiring reassurance.