A randomized clinical trial that began in 1984 was conducted to determine the efficacy of vitamin A and E supplementation to reduce the rate of disease progression in patients with retinitis pigmentosa (RP). Vitamin A was shown to provide benefit while vitamin E had an adverse effect. Although genetic testing was unavailable at that time, banked DNA samples now provide the opportunity to combine modern genetic classifications with this extensively phenotyped longitudinal cohort. We hypothesized that the beneficial effects of vitamin A would vary by genetic subtype, and that the electroretinogram (ERG) 30Hz cone flicker implicit time could serve as a biomarker to predict disease progression. Existing genetic solutions or usable DNA samples were available for 96% of subjects. The overall genetic solution rate was 587/765 (77%) of sequenced samples. Combining genetic solutions with ERG outcomes produced a coherent dataset describing the natural history of RP among patients with multiple genetic causes of disease. There were systematic differences in severity and progression seen among different genetic subtypes of RP, confirming and extending findings made for disease caused by mutations in the most common causative genes, including USH2A, RHO, RPGR, PRPF31, and EYS. Baseline 30Hz flicker implicit time was a strong predictor of progression rate. Analyses using additional data from the original trial in combination with using the implicit time as a predictive biomarker showed the deleterious effect of vitamin E on progression was still present, but surprisingly found that the effect of vitamin A progression in the cohort as a whole was not detectable. Adding additional subjects from later trials to increase power gave similar results. Subgroup analyses among the largest gene groups revealed a potential adverse effect of vitamin A supplementation in patients with disease due to mutations in the USH2A gene and a trend toward benefit in patients with the p.Pro23His mutation in the RHO gene, based only on small groups. This study also demonstrated how genetic subtype and implicit time have significant predictive power for a patient's rate of progression, which is useful prognostically. Validation of implicit time as a biomarker of disease progression, as demonstrated in this large cohort, may help with subject selection and endpoint selection in clinical trials for future experimental therapies. While vitamin E supplementation should still be avoided, these data do not support a generalized neuroprotective effect of vitamin A for all types of RP.