Abstract Purpose: Both weight loss and low-carbohydrate diets (LCD) without weight loss prolong survival in prostate cancer models. Few human trials have tested weight loss or LCD on prostate cancer. Experimental Design: We conducted a multi-site randomized 6-month trial of LCD versus control on PSA doubling time (PSADT) in patients with prostate cancer with biochemical recurrence (BCR) after local treatment. Eligibility included body mass index (BMI) ≥ 24 kg/m2 and PSADT 3 to 36 months. The LCD arm was instructed to eat \le $20 g/carbs/day; the control arm instructed to avoid dietary changes. Primary outcome was PSADT. Secondary outcomes included weight, lipids, glucose metabolism, and diet. Results: Of 60 planned patients, the study stopped early after an interim analysis showed futility. Twenty-six LCD and 19 control patients completed the study. At 6 months, although both arms consumed similar protein and fats, the LCD arm reduced carbohydrates intake (−117 vs. 6 g, P < 0.001) and lost weight (−12.3 vs. −0.60 kg, P < 0.001). The LCD arm increased HDL and reduced triglycerides and HbA1c with no difference in total cholesterol or glucose. Mean PSADT was similar between LCD (22 months) and control (15 months, P = 0.313) arms. In a post hoc exploratory analysis accounting for prestudy PSADT, baseline PSA, primary treatment, and hemoconcentration, PSADT was significantly longer in LCD versus control (30 vs. 13 months, P = 0.007) arms. Adverse events were few, usually mild, and returned to baseline by 6 months. Conclusions: Among BCR patients, LCD induced weight loss and metabolic benefits with acceptable safety without affecting PSADT, suggesting LCD does not adversely affect prostate cancer growth and is safe. Given exploratory findings of longer PSADT, larger studies testing LCD on disease progression are warranted.