AIMS:To examine the conditions under which Screening, Brief Intervention and Referral to Treatment (SBIRT) programs can be sustained by health insurance payments. DESIGN:A mathematical model was used to estimate the number of patients needed for revenues to exceed costs. SETTING:Three medical settings in the United States were examined: in-patient, out-patient and emergency department. Components of SBIRT were delivered by combinations of health-care practitioners (generalists) and behavioral health specialists. PARTICIPANTS:Practitioners in seven SBIRT programs who received grants from the US Substance Abuse and Mental Health Services Administration (SAMHSA). MEASUREMENTS:Program costs and revenues were measured using data from grantees. Patient flows were measured from administrative data and adjusted with prevalence and screening estimates from the literature. FINDINGS:SBIRT can be sustained through health insurance reimbursement in out-patient and emergency department settings in most staffing mixes. To sustain SBIRT in in-patient programs, a patient flow larger than the national average may be needed; if that flow is achieved, the range of screens required to maintain a surplus is narrow. Sensitivity analyses suggest that the results are very sensitive to changes in the proportion of insured patients. CONCLUSIONS:Screening, Brief Intervention and Referral to Treatment programs in the United States can be sustained by health insurance payments under a variety of staffing models. Screening, Brief Intervention and Referral to Treatment programs can be sustained only in an in-patient setting with above-average patient flow (more than 2500 screens). Screening, Brief Intervention and Referral to Treatment programs in out-patient and emergency department settings can be sustained with below-average patient flows (fewer than 125 000 out-patient visits and fewer than 27 000 emergency department visits).