People taking antipsychotic medications are at increased risk for obesity, diabetes, and early mortality. Few weight loss interventions have targeted this population. Thirty-six individuals were randomized to an evidence-based 12-week weight loss intervention (PREMIER with DASH diet, n = 18) or to usual care (n = 18) in this feasibility trial. Average attendance was 8.6 of 12 sessions. Intent-to-treat analyses of covariance, adjusted for baseline weight, showed significant changes in weight: Mean weight in intervention participants declined from 213.3 to 206.6 pounds, while control participants' weight was unchanged. It is possible to recruit, assess, intervene with, and retain participants taking antipsychotic medications in a dietary and exercise lifestyle change trial. Participants reported high levels of satisfaction with the intervention.