Computer tailoring and motivational interviewing show promise in promoting lifestyle change, despite few head-to-head comparative studies. Vitalum is a randomized controlled trial in which the efficacy of these methods was compared in changing physical activity and fruit and vegetable consumption in middle-aged Dutch adults. Participants (n = 1,629) were recruited via 23 general practices and randomly received either four tailored print letters, four motivational telephone calls, two of each type of intervention, or no information. The primary outcomes were absolute change in self-reported physical activity and fruit and vegetable consumption. All three intervention groups (i.e., the tailored letters, the motivational calls, and the combined version) were equally and significantly more effective than the control group in increasing physical activity (hours/day), intake of fruit (servings/day), and consumption of vegetables (grams/day) from baseline to the intermediate measurement (week 25), follow-up 1 (week 47) and 2 (week 73). Effect sizes (Cohen's d) ranged from 0.15 to 0.18. Participants rated the interventions positively; interviews were more positively evaluated than letters. Tailored print communication and telephone motivational interviewing or their combination are equally successful in changing multiple behaviors.