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Obsessive-compulsive disorder (OCD) is characterized by the presence of obsessions and/or compulsions. It is a leading cause of morbidity worldwide, as it can interfere with all aspects of life. Despite the adequate treatment trials, half of patients preserve residual or impairing symptoms and selective serotonin reuptake inhibitors (SSRIs) are not free from adverse side effects.This work aims to systematically review the current evidence available concerning the efficacy of N-acetylcysteine (NAC) in the treatment of OCD.Five randomized placebo-controlled trials (RCTs), 3 case reports and 2 case series were included. The studies developed so far are somehow contradictory. However, our pooled result from the 4 observational studies (n = 13) showed a mean reduction in Y-BOCS score after NAC treatment of −11 points (p = .01). Pooled mean difference from 4 of the 5 RCTs included was 3.35, with a95% confidence interval of −0.21-6.91 and a p-value barely below statistical significance (p = .07). This result trends to favour the use of NAC over placebo in OCD patients. NAC has an optimal tolerability profile, even in higher doses, and the most frequently reported adverse events were gastrointestinal.Despite the degree of evidence being D, in our opinion the potential of NAC is underestimated. Considering its exceptional tolerability profile, the use as an add-on agent should be contemplated, on an ad hoc basis.NAC has been studied on several psychiatric disorders as an off-label drugNAC modulates glutamatergic neurotransmission and participates in the general antioxidant activities.NAC add-on therapy might be a potential pharmacological approach to treatment-resistant OCD patients.NAC has proved an excellent tolerability profile and low-cost.