The objective was to evaluate the efficacy and safety of add-on artemether in first-episode, untreated people with schizophrenia, who were Toxoplasma gondii seropositive, and explore the change in T.gondii antibodies during treatment. In this eight-week, double-blind, randomized, placebo-controlled trial, 100 T.gondii seropositive participants with schizophrenia were randomized to either the artemether or placebo group. Participants in the artemether group received 80mg artemether once per day during the second week (days 8-14) and the fourth week (days 22-28). Participants in the placebo group received identical looking placebo capsules. Psychopathology, adverse side effects and cognitive function were measured using standardized instruments. The group×time interaction effects for the scores of the Positive and Negative Syndrome Scale (PANSS) subscales and performances on all cognitive components were not significant, only the main effect of group was significant. Compared to the placebo group, artemether group participants showed significantly greater reduction in the PANSS negative symptom scale (F(1,46)=4.7, p=0.03) and the Clinical Global Impressions Scale (F(1,96)=6.2, p=0.01) scores, but there were no significant differences in the PANSS positive symptom and general psychopathology scales (p>0.05). There were also no significant differences between the two groups in performance on any of the Brief Assessment of Cognition in Schizophrenia (BACS) cognitive domains. The artemether-risperidone combination is safe and well tolerated, but artemether as an adjunct to risperidone does not appear to alleviate cognitive deficits of schizophrenia. TRC-13003145. © 2014 Elsevier Ltd.