Background: Prostate cancer (PC) is a leading cause of cancer death in men worldwide. Imaging plays a key role in disease detection and initial staging. Emerging data has shown the superiority of ⁶⁸Gallium and ¹⁸Fluorine labeled-PSMA imaging with PET/CT over conventional imaging for primary diagnosis. Despite the success, there are challenges in meeting the high demand and expensive costs especially in low-income countries. These challenges stimulated interest in ^99mTechnetium-labeled-PSMA agents. Single photon emission computer tomography (SPECT/CT) is more worldwide available, and the imaging agent is low cost, which is more promising. The aim of this study is to compare the diagnostic accuracy of ^99mTc‐PSMA-SPECT/CT to ¹⁸F-PSMA-PET/CT in the primary diagnosis of PC and impact on clinical staging. Methods: Prospective controlled study, total of 16 patients with histologically confirmed PC (intermediate unfavorable and high risk) were recruited to undergo ¹⁸F-PSMA-PET/CT and ^99mTc-HYNIC-PSMA-SPECT/CT. Mean age of patients was 71 (54-75) years and the median PSA level was 31.5 (4.3-920) ng/ml. Lesions were divided into prostate, seminal vesicles, lymph nodes (LN) (locoregional [LR] and non-locoregional [NLR]), bone, and visceral metastases. The size of LN with PSMA avidity on ^99mTc‐PSMA-SPECT/CT were determined. Lesions detected were read independently of PET/CT findings with two experienced nuclear medicine physicians. Volumetric analysis was also performed between the two imaging modalities (Tumoral Total Volume [TTV]) and correlated with PSA levels. Results: A total of 233 lesions were detected on ¹⁸F-PSMA-PET/CT; prostate (n=16), seminal vesicles (n=11), LN LR (n=54), NLR (n=66), bone (n=82) and visceral (n=4); of these ^99mTc‐PSMA-SPECT/CT both reviewers detected 100% of the lesions in prostate (16/16), seminal vesicles (11/11) and visceral (4/4); LN LR (51/54; 94%), NLR (51/66; 77%) and bone (70/82; 85%). Between reviewers there was discordance in just 3 LN (<4 mm) and 1 bone metastases. The lowest diameter of positive LN detected by SPECT/CT was 4 mm (range 4-18). Pearson-correlation coefficient between PSA and TTV SPECT was r=0.68 (p=0.003) and for TTV PET r=0.71 (p=0.002). There were not statistically significant differences between TTV SPECT and TTV PET (T-student p=0.48). Five cases with high volume disease were detected by both methods. All patients were classified according to miTNM showing no difference. Conclusions:^99mTc‐PSMA-SPECT/CT may be a useful in primary diagnosis of PC. Despite it showed a slightly lower lesion detection rate compared to ¹⁸F-PSMA-PET/CT, it exhibited no impact on clinical staging and consequently the initial treatment intension. Our results show that ^99mTc‐PSMA-SPECT/CT could be used as a cost-efficient alternative with wider availability and no significant difference.