In total, 70 smokers will be randomized to: standard of care smoking cessation medication varenicline alone (an FDA-approved smoking cessation medication) or varenicline plus contingency management (CM) (a behavioral procedure with rewards for target behaviors, like smoking abstinence). Patients in both conditions will receive varenicline for 12 weeks with standard smoking cessation therapy and regular breath and urine sample monitoring for smoking. Patients assigned to CM will earn chances to win prizes for each breath sample that tests negative for smoking, and urine samples that test negative for smoking will result in even greater chances for prizes. More CM patients are expected to achieve and maintain abstinence than patients receiving varenicline alone.

Inclusion Criteria:

• smoke >10 cigarettes/day, with no abstinent period exceeding 3 months in past year
• expired CO of >8 ppm
• self-reported desire to stop smoking
• >18 years of age
• resting systolic BP<160 mmHg and diastolic BP<100 mmHg and otherwise in good health
• if on antihypertensive medication, have not changed medications in the past month and do not intend to change in next 3 months
• English speaking

Exclusion Criteria:

• receipt of smoking cessation treatment (behavioral or pharmacological) in past month
• serious or unstable medical disease in past 6 months, including myocardial infarction, cancer, congestive heart failure, kidney failure, stroke, or seizures
• evidence or history of allergic reactions contraindicating varenicline or clinically significant laboratory or electrocardiographic (ECG) abnormalities
• breastfeeding, pregnant or not using effective contraception if a woman of childbearing potential
• arm circumference of >42 cm
• serious psychiatric illness in past 6 months (e.g., schizophrenia, psychosis, suicide risk, drug or alcohol dependence other than nicotine)
• use of tobacco containing products other than cigarettes in past month and do not agree to abstain from use of these products during study participation
• ongoing use of any of the following medications: nicotine replacement therapies, monoamine oxidase inhibitors, antipsychotics, mood stabilizers, or naltrexone
• in recovery for pathological gambling, due to potential similarity with prize CM, although no increases in gambling have been noted