Background: Current guidelines recommend treatment of metabolic acidosis in chronic kidney disease (CKD) with sodium-based alkali. We tested the hypothesis that treatment with base-producing fruits and vegetables (F + V) better improves cardiovascular disease (CVD) risk indicators than oral sodium bicarbonate (NaHCO<sub>3</sub>). Methods: We randomized 108 macroalbuminuric, matched, nondiabetic CKD patients with metabolic acidosis to F + V ( n = 36) in amounts to reduce dietary acid by half, oral NaHCO<sub>3</sub> (HCO<sub>3</sub>, n = 36) 0.3 mEq/kg bw/day, or to Usual Care (UC, n = 36) to assess the 5-year effect of these interventions on estimated glomerular filtration rate (eGFR) course as the primary analysis and on indicators of CVD risk as the secondary analysis. Results: Five-year plasma total CO<sub>2</sub> was higher in HCO<sub>3</sub> and F + V than UC but was not different between HCO<sub>3</sub> and F + V (difference p value < 0.01). Five-year net eGFR decrease was less in HCO<sub>3</sub> (mean –12.3, 95% CI –12.9 to –11.7 mL/min/1.73 m<sup>2</sup>) and F + V (–10.0, 95% CI –10.6 to –9.4 mL/min/1.73 m<sup>2</sup>) than UC (–18.8, 95% CI –19.5 to –18.2 mL/min/1.73 m<sup>2</sup>; p value < 0.01) but was not different between HCO<sub>3</sub> and F + V. Five-year systolic blood pressure was lower in F + V than UC and HCO<sub>3</sub> ( p value < 0.01). Despite similar baseline values, F + V had lower low-density lipoprotein, Lp(a), and higher serum vitamin K1 (low serum K1 is associated with coronary artery calcification) than HCO<sub>3</sub> and UC at 5 years. Conclusion: Metabolic acidosis improvement and eGFR preservation were comparable in CKD patients treated with F + V or oral NaHCO<sub>3</sub> but F + V better improved CVD risk indicators, making it a potentially better treatment option for reducing CVD risk.