Objective To determine whether lutein supplementation will slow visual function decline in patients with retinitis pigmentosa receiving vitamin A. Design Randomized, controlled, double-masked trial of 225 non-smoking patients, age 18-60 years, evaluated over a 4-year interval. Patients received lutein 12 mg or a control tablet daily. All were given vitamin A palmitate 15,000 IU/day. Randomization took into account genetic type and baseline serum lutein. Main Outcome Measures The primary outcome was the total point score for the Humphrey Field Analyzer (HFA) 30-2 program; pre-specified secondary outcomes were the total point scores for the 60-4 program and for the 30-2 and 60-4 combined, 30-Hz electroretinogram amplitude, and ETDRS acuity. Results No significant difference in rate of decline was found between the lutein + A and control + A groups over a 4-year interval for the HFA 30-2 program. For the HFA 60-4 program a decrease in mean rate of sensitivity loss was observed in the lutein + A group (p=0.05). Mean decline with the 60-4 program was slower among those with the highest serum lutein or with the highest increase in macular pigment optical density (MPOD) at follow-up (p= 0.01 and p=0.006 respectively). Those with the highest increase in MPOD also had the slowest decline in 30-2 and 60-4 combined field sensitivity (p=0.005). No significant toxic side effects of lutein supplementation were observed. Conclusion Lutein supplementation 12 mg/d slowed loss of midperipheral visual field on average among nonsmoking adults with retinitis pigmentosa taking vitamin A. Application to Clinical Practice Data are presented that support use of lutein 12 mg/day to slow visual field loss among non-smoking adults with retinitis pigmentosa on vitamin A. Trial Registry Randomized Clinical Trial for Retinitis Pigmentosa, NCT00346333, www.ClinicalTrial.gov