Previous results from the investigators' Center have shown that combination treatment with Chantix and Zyban is more successful in helping men quit smoking. The investigators hope to replicate these findings with this study.

Inclusion Criteria:

• Have no known serious medical conditions;
• Male;
• Are 18-65 years old;
• Smoke an average of at least 10 cigarettes per day;
• Have smoked at least one cumulative year;
• Have an expired air carbon monoxide (CO) reading of at least 10ppm;
• Able to read and understand English;
• Express a desire to quit smoking in the next thirty days.

Potential subjects must agree to use acceptable contraception.

Potential subjects must agree to avoid the following:

• participation in any other nicotine-related modification strategy outside of this protocol;
• use of tobacco products other than cigarettes, including pipe tobacco, cigars, e-cigarettes, snuff, and chewing tobacco;
• use of experimental (investigational) drugs or devices;
• use of illegal drugs;
• use of opiate medications.

Exclusion Criteria:

• Hypertension;
• Hypotension with symptoms;
• Coronary heart disease;
• Lifetime history of heart attack;
• Cardiac rhythm disorder (irregular heart rhythm);
• Chest pains (unless history, exam, and electrocardiogram (ECG) clearly indicate a non-cardiac source);
• Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
• History of skin allergy;
• Active skin disorder (e.g., psoriasis) within the last five years;
• Liver or kidney disorder (except kidney stones, gallstones);
• Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;
• Active ulcers in the past 30 days;
• Currently symptomatic lung disorder/disease (including but not limited to Chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
• Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
• Migraine headaches that occur more frequently than once per week;
• Recent, unexplained fainting spells;
• Problems giving blood samples;
• Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%);
• Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
• Other major medical condition;
• Current psychiatric disease (with the exception of anxiety disorders, Obsessive Compulsive Disorder (OCD) and ADHD);
• Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide;
• Current depression;
• Bulimia or anorexia;
• Use of opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed) within the past 14 days;
• Smoking more than one cigar a month.
• Alcohol abuse;
• Significant adverse reaction to nicotine patches, bupropion / Wellbutrin / Zyban or Chantix / varenicline in the past.
• Current participation or recent participation (in the past 30 days) in another smoking study at our Center or another research facility.
• Current participation in another research study.

Use (within the past 30 days) of:

• Illegal drugs (or if the urine drug screen is positive for tetrahydrocannabinol (THC), Cocaine, Amphetamine, Opiates, Methamphetamines, phencyclidine (PCP), Benzodiazepines, or Barbiturates),
• Experimental (investigational) drugs;
• Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
• Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes;
• Wellbutrin, bupropion, Zyban, Chantix, varenicline, nicotine replacement therapy or any other smoking cessation aid.

Subjects (subjs.) received (rcvd.) study drugs for 13 weeks. At each study session during this period subjs. completed a questionnaire about side effects (SE). Subjs. were also told to contact study staff between study sessions if SE were bothersome.

Serious Adverse Events (AE) were evaluated for all subjs. who rcvd. nic. patches at Visit (V) 1 (197), & subjs. randomized to receive Chantix (90) or Chantix+Zyban (84) at V2. Other AEs were evaluated for all subjs. receiving nic. patches & completing V2 SE quest. (176), & randomized subjs. completing SE quest. at V3 (170) & at subsequent visits.