Objectives: This study assessed specific dietary practices and overall physical activity patterns of Lakota adults residing on Indian reservations in South Dakota. Perceived barriers to changing dietary and physical activity behaviors were also examined. Design: A convenience sample of Lakota adults was surveyed. Data on consumption of higher-fat foods, fruit and vegetable intake, use of sugar-sweetened beverages, physical activity patterns, and barriers to change in diet and physical activity were collected via in- person interviews. Subjects/setting: A total of 219 adults from 2 adjacent reservations in South Dakota participated. Results: Higher-fat foods consumed most frequently included margarine and butter (32.0% ≥ 5 times per week); eggs (30.1% ≥ 5 times per week); whole milk (25.7% ≥ 5 times per week); potato chips, corn chips, and popcorn (15.1% ≥ 5 times per week); and bacon and sausage (13.3% ≥ 5 times per week). Few subjects reported consuming fruit on a daily basis. Vegetables were consumed somewhat more frequently. Most subjects reported engaging in mild or moderate physical activities 3 or more times per week, although women were found to engage in moderate and strenuous physical activities less frequently than men. Major barriers to fruit intake included expense (16.4%), quality (14.2%), and availability (13.2%). Barriers to vegetable intake mentioned most frequently included availability (11.4%), cost (10.4%), and quality (9.1%). Taste was the most frequently mentioned barrier to cutting intake of high-fat foods (27.9%). Lack of child care (I5.8%), lack of time (14.7%), and safety concerns (14.6%) were the most salient barriers to regular exercise. Applications/conclusions: Nutrition interventions are needed that address the major barriers to diet change reported by Lakota adults. Efforts to increase physical activity should focus on Lakota women and should address the identified barriers to regular exercise.