Phase III randomized, 2 x 2 design, open label, multi-center study that will assess the removal of filter ventilation on smoking behavior and biomarkers in a tobacco and nicotine product marketplace simulation of a real world environment.

This randomized, open label, controlled multi-site study will simulate a "real world" tobacco environment by providing access to an experimental marketplace where they will be given vouchers that can be exchanged for assigned study cigarettes (either ventilated or unventilated) and two of the groups will also have access to non-combusted tobacco/nicotine products.

Subjects (N=550; N=125 in each group) will be randomly assigned to: 1) Ventilated cigarettes only; or 2) Unventilated cigarettes only; 3) Ventilated cigarettes + alternative nicotine delivery systems (ANDS); 4) Unventilated cigarettes + ANDS.

Smokers will undergo an in person screening and then a 12 week experimental trial consisting of 2 weeks of baseline; 2 weeks of usual brand cigarettes in the marketplace and 8 weeks on the study cigarettes in the marketplace, plus a follow-up visit 4 weeks after the intervention is over. The experimental period will simulate a "real world" environment by providing participants with vouchers for a specified number of points that can be exchanged for study cigarettes and/or ANDS. At the end of the study they can exchange unspent points for money.

Biomarker samples (total nicotine equivalents, tobacco specific nitrosamines, volatile organic compound and inflammation markers), smoking topography and inhalation measures are taken at baseline and end of trial.

Inclusion Criteria:

• At least 18 years of age
• Biochemically confirmed regular cigarette smoker

Exclusion Criteria:

• Unstable health
• Unstable medications
• Pregnant or nursing

Intend to share findings from this research through publications and presentations. Institutions and individuals wishing to access any resources or data must contact the Principal Investigator (Hatsukami). Data generated by this grant will be made to outside investigators, according to NIH Guidance. When data are shared, there will be no limits placed on how the data will be used. Users will agree, however, that the recipient must not transfer the data to other users and that the data are only to be used for research purposes. A record of transfer of data and a copy of the dataset that was distributed will be kept by University of Minnesota.

Data will not be available until primary and secondary papers are accepted for publication.

Persons requesting data must do so in writing, identifying their affiliation and how the data will be used. Upon review, access will be determined.