Medifast 5 & 1 Plan

Inclusion Criteria: * BMI 35-50 kg/m2 * Interested in weight loss * Computer with internet access * Any race or ethnicity * Fasting glucose \<126 mg/dL at screening Exclusion Criteria: * Participation in any weight-reduction program, weight-loss diet, or other special diet within the previous 3 months. * Weight loss or gain of \>5% body weight in past 6 months for any reason except post-partum weight loss. * Currently taking any medication that suppresses or stimulates appetite. * History of prior surgical procedure for weight control or liposuction. * Current smoker or quit smoking less than 6 months prior. * Any major disease, including: * Active cancer or cancer requiring treatment in the past 2 years (except nonmelanoma skin cancer). * Active or chronic infections, including self-reported HIV positivity and active tuberculosis. * Active cardiovascular disease or event including hospitalization or therapeutic procedures for treatment of heart disease (e.g., coronary artery bypass, percutaneous transluminal coronary angioplasty) in the past 6 months; New York Heart Association Functional Class \>2 with respect to congestive heart failure; stroke or transient ischemic attack in the past 6 months. * Uncontrolled hypertension: systolic blood pressure \>160 mm Hg or diastolic blood pressure \>95 mm Hg on treatment. * Gastrointestinal disease, including self-reported chronic hepatitis or cirrhosis, any episode of alcoholic hepatitis or alcoholic pancreatitis within past year, inflammatory bowel disease requiring treatment in the past year, recent or significant abdominal surgery (e.g., gastrectomy). * Active kidney disease. * Lung disease: chronic obstructive airway disease requiring use of oxygen. * Diagnosed diabetes (type 1 or 2), fasting hyperglycemia (blood glucose \>126 mg/dL), or use of any anti-diabetic medications. * Uncompensated or uncontrolled psychiatric disease (such as schizophrenia and bipolar disorder) that, in opinion of the investigators, would impede conduct of the trial or completion of procedures. * A score on the Brief Symptom Inventory (BSI) (Derogatis \& Melisaratos, 1983) that exceeds the 90th percentile. * History of or current eating disorders, or an Eating Attitudes Test (EAT 40) score \>30. * Active food allergies, particularly to wheat, gluten, soy or nuts. * Conditions or behaviors likely to effect the conduct of the trial: unable or unwilling to give informed consent; unable to communicate with the pertinent clinic staff; another household member is a participant or staff member in the trial; unwilling to accept treatment assignment by randomization; current or anticipated participation in another intervention research project that would interfere with the intervention offered in the trial; likely to move away from participating clinics before trial completed; unable to walk 0.25 mile in 10 minutes. * Currently taking antidepressant, steroid, or thyroid medication, unless dosage is stable. * No regular source of health care. * Any active use of illegal or illicit drugs or history of illegal or illicit drug utilization within past year * Excessive alcohol intake, either acute or chronic defined as any one of the following: 1) average consumption of 3 or more alcohol containing beverages daily; 2) consumption of 7 or more alcoholic beverages within a 24-hr period in the past 12 months; or 3) other evidence available to clinic staff. * Willing to limit alcohol intake to zero * Pregnancy and childbearing: currently pregnant or less than 3 months post partum; currently nursing or within 6 weeks of having completed nursing; pregnancy anticipated during study; unwilling to report possible or confirmed pregnancies promptly during the course of the trial; unwilling to take adequate contraceptive measures if potentially fertile. * Any other conditions which, in opinion of the investigators, would adversely affect the conduct of the trial.