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RATIONALE AND OBJECTIVES To investigate radiation dose reduction during whole body fluorodeoxyglucose (18F-FDG) positron emission tomographic (PET)/computed tomography (CT) by employing weight-based protocols. MATERIALS AND METHODS One thousand and twenty-eight patients were referred for 18F-FDG PET/CT study with one of two protocols: conventional protocol I; 120 kVp, 120 mAs, 0.5 second rotation time, pitch 0.8 mm/rot across all body weights; four-tier body weight protocol II all used 140 kVp, 0.75 seconds rotation time and pitch 0.8 mm/rot: Protocol A (≤60 kg): 35 mAs, Protocol B (61-80 kg): 50 mAs, Protocol C (81-100 kg): 65 mAs, and Protocol D: (>101 kg): 100 mAs. All protocols employed tube current modulation. Quantitative and qualitative image visual grading characteristics assessed image quality. RESULTS Patient demographics demonstrated no significant difference between each protocol except for patient weight in weight protocol IIB (p < 0.009). Mean effective dose in all protocols were significantly lower in Protocol B compared to A (p < 0.009). Contrast-to-noise ratio demonstrated no differences between each protocol (p < 0.21) except for weight protocol in protocol IIA (<60 kg, p = 0.035) with the visual grading characteristics demonstrating preference over protocol II compared to I. CONCLUSION Significant reduction in radiation dose can be achieved using patient-specific body weight-based protocols during whole-body 18F-FDG PET/CT without compromising image quality when employing weight-based protocols.