Background: Introduction: Determination of the type of treatment and prognosis of epididymoorchitis is a challenge for clinicians. Objectives: The current study aimed at investigating the relationship between the indexes of vascular resistance index (RI) (%) of the intra-testicular artery by color Doppler ultrasonography (CDUS), and its relationship with the treatment and prognosis in patients with epididymo-orchitis. Patients and Methods: The current prospective observational study was conducted on the collected data of 30 patients with epididymo-orchitis. Initial and secondary CDUS (24 hours after admission) were conducted on all patients and RI was calculated from the mean of two intratesticular arteries for all patients. Patients were divided into four groups based on RI through, RI; 70-80%, RI; 80- 90%, RI >90%, and absent of flow. Results: The mean and standard deviation (SD) of the patients’ age was 47.70 ± 15.56 years (ranged 30-79 years). Among 30 patients, 15 (50%) had left epididymo-orchitis, 13 (43.5%) right, and in two subjects (6.71%), it was bilateral. The mean ± SD of RI in the initial and secondary CDUS were 0.8516 ± 0.1022% and 0.7845 ± 0.1235%, respectively (P=0.031). The ROC under area of RI diagnosis power for the types of epididymo-orchitis treatment were 0.904 [95% confidence interval (CI): 0.774-1.000] and 0.990 (95%CI: 0.958-1.000) in the initial and second day of CDUS, respectively. Additionally, the mean ± SD of RI in initial CDUS were 0.7633 ± 0.03786%, 0.84400 ± 0.02944%, and 0.7600 ± 0.03162% in patients with a decreased prognosis, atrophy, and parenchymal heterogeneity, which were significantly different (P= 0.011). Accordingly, in the CDUS of 24 hours after admission, the mean ± SD of RI in patients with low prognosis was 0.6600 ± 0.0100%, in patients with atrophy was 0.0170 ± 0.7575%, and in patients with parenchymal heterogeneity was 0.7100 ± 0.04729%. Conclusion: RI of intratesticular artery in CDUS is a useful index to determine and predict the type of treatment and prognosis of patients with epididymo-orchitis.