Schizophrenia which is a chronic disabling burdensome psychotic disorder has been treated with different antipsychotic medications. Some studies have reported a possible correlation between deficiency in minerals, nutrients and vitamins - mainly group B vitamins - and the development of schizophrenia. In the present study, we aimed to examine the effect of the B vitamin group as an adjuvant treatment to antipsychotics in individuals with chronic schizophrenia. In a randomized, double-blind clinical trial study, involving two groups of 25 patients with chronic schizophrenia, we compared the effects of a 12-week adjuvant treatment with a combination of B vitamins - B1 (15mg), B2 (15mg), B6 (10mg), B12 (10µg) and nicotinamide (50 mg) - with a placebo. The impact on negative, positive and cognitive symptoms of schizophrenia was assessed for both groups before the intervention (T0) and at 4, 8 and 12 weeks after the intervention (T1, T2, and T3, respectively). Following the treatment, negative symptoms scores decreased in the treatment group at 12 weeks following the beginning of the treatment (F (4, 45) = 464.7, P < 0.0001). Although a trend toward improvement in positive symptoms and cognitive scores was seen, these changes were not significant. Our results suggest that selecting the group B vitamins as an adjuvant treatment to the antipsychotics may have beneficial effects on improving negative symptoms of patients with chronic schizophrenia.