Despite the high prevalence in patients with schizophrenia, the association of cannabis and nicotine use with negative symptoms remains unclear. We performed a meta-analysis of observational studies addressing the association of cannabis and nicotine use with negative symptoms. Twenty cannabis studies (n = 2611) and 45 nicotine studies (n = 8942) were analyzed. There was no significant effect for current cannabis use alone or in combination with other substances. However, recently abstinent users of cannabis showed less severe negative symptoms than nonusers. Nicotine users were not different from nonusers with respect to negative symptoms. With respect to positive symptoms, very small increases were found for cannabis users and patients using nicotine along with other drugs. In conclusion, while patients with schizophrenia who use cannabis did not differ from nonusers, recently abstinent patients showed less severe negative symptoms than nonusers. This finding suggests that cannabis-using patients might be less susceptible to the development of negative symptoms. The amotivational effects of cannabis may obscure these differences in current users.