The purpose of this study was to examine the effects of smokeless tobacco (ST) brand switching on biomarkers of ST exposure and on ST use. Subjects seeking treatment to reduce their use were randomized to ST brand switching with controlled ST topography, brand switching with ad libitum ST use, or a waitlist control with subsequent randomization to one of these two conditions. The waitlist control group was included to assess whether changes were a consequence of time effect. During the intervention, Copenhagen or Kodiak ST users were asked to switch to products that were sequentially lower in nicotine content: Skoal Long Cut Straight or Wintergreen for 4 weeks and then Skoal Bandits for the subsequent 4 weeks. Measures were obtained during the course of treatment and at 12-week follow-up. Significant reductions in total urinary cotinine and 4-(methylnitrosamino)-L-(3-pyridyl)-L-butanol (NNAL) plus its glucuronides (total NNAL) were observed with no significant differences between the controlled topography and ad libitum conditions. Significant reductions were also observed in the amount and duration of dips with a significant intervention effect for durational measures. At 12 weeks, the 7-day biochemically-verified tobacco abstinent rate was 26% in the ad libitum group. ST brand switching may be a feasible alternative intervention for ST users interested in quitting but unwilling to stop ST use completely.