Although small-scale studies have described the effects of oxytocin on social deficits in autism spectrum disorder (ASD), no large-scale study has been conducted. In this randomized, parallel-group, multicenter, placebo-controlled, double-blind trial in Japan, 106 ASD individuals (18-48 y.o.) were enrolled between Jan 2015 and March 2016. Participants were randomly assigned to a 6-week intranasal oxytocin (48IU/day,n = 53) or placebo (n = 53) group. One-hundred-three participants were analyzed. Since oxytocin reduced the primary endpoint, Autism Diagnostic Observation Schedule (ADOS) reciprocity, (from 8.5 to 7.7;P < .001) but placebo also reduced the score (8.3 to 7.2;P < .001), no between-group difference was found (effect size -0.08; 95% CI, -0.46 to 0.31;P = .69); however, plasma oxytocin was only elevated from baseline to endpoint in the oxytocin-group compared with the placebo-group (effect size -1.12; -1.53 to -0.70;P < .0001). Among the secondary endpoints, oxytocin reduced ADOS repetitive behavior (2.0 to 1.5;P < .0001) compared with placebo (2.0 to 1.8;P = .43) (effect size 0.44; 0.05 to 0.83;P = .026). In addition, the duration of gaze fixation on socially relevant regions, another secondary endpoint, was increased by oxytocin (41.2 to 52.3;P = .03) compared with placebo (45.7 to 40.4;P = .25) (effect size 0.55; 0.10 to 1.0;P = .018). No significant effects were observed for the other secondary endpoints. No significant difference in the prevalence of adverse events was observed between groups, although one participant experienced temporary gynecomastia during oxytocin administration. Based on the present findings, we cannot recommend continuous intranasal oxytocin treatment alone at the current dose and duration for treatment of the core social symptoms of high-functioning ASD in adult men, although this large-scale trial suggests oxytocin's possibility to treat ASD repetitive behavior.