The effects of B vitamins and/or ω-3 fatty acids on cancer outcomes were investigated in cardiovascular disease survivors participating in the French Supplementation With Folate, Vitamins B6 and B12, and/or Omega-3 Fatty Acids trial. This was a secondary analysis of data from 2501 individuals aged 45 to 80 years, randomized in a 2 × 2 factorial design to 1 of 4 daily supplementation groups. After 5 years of supplementation, incident cancer was validated in 7% of the sample (145 events in men and 29 in women), and cancer mortality occurred in 2.3% of the sample. Cox proportional hazards models showed no association between supplementation with B vitamins and/or ω-3 fatty acids and cancer incidence or mortality. There was a statistically significant interaction of treatment by sex, with no effect of treatment on cancer risk among men and increased cancer risk among women for ω-3 fatty acids supplementation (hazard ratio, 3.02; 95% CI, 1.33-6.89). Overall, no beneficial effects of supplementation with relatively low doses of B vitamins and/or ω-3 fatty acids were found regarding cancer outcomes in individuals with cardiovascular disease history.