Alcohol misuse among college students is a public health concern. Protective behavioral strategies (PBS) can be used before, during, after, or instead of drinking to reduce alcohol use and negative consequences, but findings on their utility at the aggregate level are mixed. Although recent work has provided important information on the performance of individual PBS items, it is limited by research designs that are cross-sectional, do not examine consequences, or do not examine other important correlates, such as drinking motives. This study examines both the association between item-level PBS and alcohol-related negative consequences and the moderating effect of drinking motives longitudinally. College students from two universities (n = 200, 62.5% female, Mage = 20.16) completed the Drinking Motives Questionnaire-Revised, Protective Behavioral Strategies Survey, the Rutgers Alcohol Problem Index, and a measure of the quantity of alcohol use at baseline and 3-month follow-up. Generalized linear models were conducted to assess direct effects of item-level PBS on alcohol-related consequences and the moderating effects of drinking motives. Two PBS items were associated with fewer alcohol-related consequences at follow-up, and two items were associated with greater alcohol-related consequences at follow-up. Drinking motives differentially moderated associations between item-level PBS and alcohol-related consequences for a proportion in the sample. Enhancement motives moderated the greatest number of associations, followed by coping, conformity, and social motives. Certain PBS (e.g., drink slowly, rather than gulp or chug) were moderated by several drinking motives, whereas other PBS items were not moderated by any motives. Consistent with previous research, some item-level PBS were associated longitudinally with increased negative consequences, and some were associated with decreased negative consequences. Drinking motives, particularly enhancement, moderated several item-level PBS and consequence associations, suggesting that reasons for drinking may be important for understanding the associations between PBS strategies and alcohol-related consequences.