Background: Risperidone produces marked adverse effects including weight gain which often causes patients to discontinue the treatment. However, if patients continue to receive further treatment, increasing weight gain was found to increase a risk of clinically significant obesity and several health problems. Objective: To investigate the factors associated with risperidone-related weight gain in Thai autistic spectrum disorder patients. Methods: We conducted a retrospective and observational study among Thai autistic patients treated with risperidone. The data collected included risperidone dose, sex, age, body weight and BMI baseline, concomitant drug therapy, duration of drug used, and phenotype/genotype of CYP2D6 responsible for body weight gain during risperidone therapy. Results: Univariate analysis showed that factors affecting the body weight gain among risperidone-treated Thai autistic patients were duration of risperidone treatment (months) (P<0.0001), cumulative dose (P<0.0001), age (P=0.001) and BMI baseline (P<0.01). Multivariable analysis showed that factors affecting the body weight gain were duration of treatment (months) (P=0.011), baseline age (P=0.002) and age (P<0.0001). Conclusions: This study makes a preliminary contribution to provide opportunities for personalized medicine in the predictive assessment of weight gain and to minimize the risk for metabolic syndrome in risperidone-treated Thai patients.