This study aimed to compare weight loss (WL) outcomes for patients taking antidepressants and/or antipsychotics with those not taking psychiatric medication.A total of 17,519 adults enrolled in a lifestyle WL intervention at the Wharton Medical Clinics in Ontario, Canada, were analyzed. Sex-stratified multivariable linear regression analysis was used to examine the association of taking antidepressants, antipsychotics, both, or neither with WL when adjusting for age, initial weight, and treatment time.Twenty-three percent of patients were taking at least one psychiatric medication. Patients lost a significant amount of weight (P < 0.0001) regardless of psychiatric medication use. Women taking psychiatric medications lost a similar amount of weight as women who were not (P > 0.05). Conversely, men taking antidepressants lost only slightly less weight than men taking both classes or neither class of psychiatric medication (3.2 ± 0.3 kg vs. 5.6 ± 0.9 kg and 4.3 ± 0.1 kg; P < 0.05). However, taking psychiatric medications that cause weight gain was associated with similar significant decreases in weight as taking medications that are weight neutral or associated with WL for both sexes (P > 0.05).Results of this study suggest that those who participate in a weight management program can lose significant amounts of weight regardless of psychiatric medication use.