Inclusion Criteria:

• Males and females, 18 to 65 years old.
• Meets DSM-IV criteria for Cocaine Dependence, as determined by the Structured Clinical Interview for DSM-IV (SCID).
• Live within a commutable distance of the Treatment Research Center (TRC) at the Penn/VA Center for Studies of Addiction, University of Pennsylvania. We define this to be a distance within the service area of Septa, within an hour drive, or a distance that both the patient and Principal Investigator (PI) find acceptable.
• Understands and signs the informed consent.

Exclusion Criteria:

• Current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine or nicotine dependence, as determined by the SCID.
• Concomitant treatment with psychotropic medications.
• Current or prior gambling problems. This will be assessed by the patient's self-report.
• Patients mandated to treatment based upon a legal decision or as a condition of employment. This will be assessed by the patient's self-report.
• Current severe psychiatric symptoms, e.g., psychosis, dementia, suicidal or homicidal ideation, mania or depression requiring antidepressant therapy in the opinion of the Principal Investigator (PI)
• Use of any investigational medication within the past 30 days.
• History of significant heart disease (an arrhythmia which required medication, Wolff-Parkinson -White Syndrome, angina pectoris, documented history of myocardial infarction, heart failure).
• History of chest pain associated with cocaine use that has prompted a visit to a physician.
• Current use of naltrexone, disulfiram, modafinil, stimulants, reserpine, verapamil, theophylline, trimethoprim, cimetidine, haloperidol, benzodiazepines or anticonvulsants.
• Known hypersensitivity to varenicline.
• Patients with known AIDS or other serious illnesses that may require hospitalization during the study.
• Female subjects who are pregnant or lactating, or female subjects of child-bearing potential who are not using acceptable methods of birth control.

Acceptable methods of birth control include:

• barrier (diaphragm or condom) with spermicide
• intrauterine progesterone contraceptive system
• levonorgestrel implant
• medroxyprogesterone acetate contraceptive injection
• oral contraceptives.
• tubal ligation.
• Patients with impaired renal function as indicated by corrected creatinine clearance below 80 ml/min/70 kg as determined by the modified Cockcroft equation (CDC, 1986).
• Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits that are clinically unacceptable to the Principal Investigator.

EKG 1st degree heart block, sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes are allowed; liver function tests [LFTs] <5 x ULN are acceptable).