Abstract Background Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) has become an increasingly established imaging modality in the staging of prostate cancer (PCa). Numerous PSMA-based tracers are currently available, however, there is a lack of consensus on the optimal radiotracer(s) for PSMA PET/CT. This study aims to investigate whether Fluorine-18 (¹⁸F)-labelled PSMA PET/CT is significantly different from Gallium-68 (⁶⁸Ga) in primary diagnosis and/or secondary staging of prostate cancer following biochemical recurrence. Methods A critical review of MEDLINE, EMBASE, PubMed and Web of Science databases was performed in May 2023 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Studies that directly compared ¹⁸F-based PSMA radiotracers and [⁶⁸Ga]Ga-PSMA-11 in terms of the normal organ SUV or the lesion SUV or the detection rate were assessed. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Results Twenty-four studies were analysed. [¹⁸F]DCFPyL and [¹⁸F]PSMA-1007 were the two most commonly studied ¹⁸F based PSMA tracers. [¹⁸F]JK-PSMA-7, [¹⁸F]rhPSMA-7, [¹⁸F]AlF-PSMA-11 were the new tracers evaluated in a limited number of studies. Overall, [¹⁸F]DCFPyL was observed to have a similar lesion detection rate to [⁶⁸Ga]Ga-PSMA-11 with no increase in false positive rates. [¹⁸F]PSMA-1007 was found to have a greater local lesion detection rate because of its predominant hepatobiliary excretory route. However, [⁶⁸Ga]Ga-PSMA-11 was observed to have a similar local lesion detection rate in studies that administer patients with furosemide prior to the scan. In addition, [¹⁸F]PSMA-1007 was found to have a significant number of benign bone uptakes. Conclusions [¹⁸F]DCFPyL was observed to be similar to [⁶⁸Ga]Ga-PSMA-11. [¹⁸F]PSMA-1007 was observed to be less preferrable to [⁶⁸Ga]Ga-PSMA-11 due to its high benign bone uptakes. Overall, there was not enough evidence in differentiating the radiotracers based on their clinical impacts.