Background: Prevention of weight gain has been suggested as an important strategy in the prevention of obesity and people who are overweight are a specifically important group to target. Currently there is a lack of weight gain prevention interventions that can reach large numbers of people. Therefore, we developed an Internet-delivered, computer-tailored weight management intervention for overweight adults. The focus of the intervention was on making small (100 kcal per day), but sustained changes in dietary intake (DI) or physical activity (PA) behaviors in order to maintain current weight or achieve modest weight loss. Self-regulation theory was used as the basis of the intervention. Objective: This study aims to evaluate the efficacy of the computer-tailored intervention in weight-related anthropometric measures (Body Mass Index, skin folds and waist circumference) and energy balance-related behaviors (physical activity; intake of fat, snacks and sweetened drinks) in a randomized controlled trial. Methods: The tailored intervention (TI) was compared to a generic information website (GI). Participants were 539 overweight adults (mean age 47.8 years, mean Body Mass Index (BMI) 28.04, 30.9% male, 10.7% low educated) who where recruited among the general population and among employees from large companies by means of advertisements and flyers. Anthropometric measurements were measured by trained research assistants at baseline and 6-months post-intervention. DI and PA behaviors were assessed at baseline, 1-month and 6-month post-intervention, using self-reported questionnaires. Results: Repeated measurement analyses showed that BMI remained stable over time and that there were no statistically significant differences between the study groups (BMI: TI=28.09, GI=27.61, P=.09). Similar results were found for waist circumference and skin fold thickness. Amount of physical activity increased and intake of fat, snacks and sweetened drinks decreased during the course of the study, but there were no differences between the study groups (eg, fat intake: TI=15.4, GI=15.9, P=.74). The first module of the tailored intervention was visited by almost all participants, but only 15% completed all four modules of the tailored intervention, while 46% completed the three modules of the general information intervention. The tailored intervention was considered more personally relevant (TI=3.20, GI=2.83, P=.001), containing more new information (TI=3.11, GI=2.73, P=.003) and having longer texts (TI=3.20, GI=3.07, P=.01), while there were no group differences on other process measures such as attractiveness and comprehensibility of the information (eg, attractive design: TI=3.22, GI=3.16, P=.58). Conclusions: The online, computer-tailored weight management intervention resulted in changes in the desired direction, such as stabilization of weight and improvements in dietary intake, but the intervention was not more effective in preventing weight gain or modifying dietary and physical activity behaviors than generic information. A possible reason for the absence of intervention effects is sub-optimal use of the intervention and the self-regulation components. Further research is therefore needed to gain more insight into how the intervention and exposure to its contents can be improved.