Long-term effects of paratuberculosis on within-herd prevalence and on-farm economy of implementing risk-based control strategies were compared with alternative strategies by using a herd-simulation model. Closing transmission routes is essential for effective control of paratuberculosis. However, many farmers lack the resources to carry out these procedures for all cows in the herd. When using risk-based control strategies 1) all cows are tested quarterly with a milk ELISA, 2) specific cows with a high risk of being infectious are identified, and 3) the farmer can focus only on these infectious animals to close infection routes. In this way the workload can be reduced, making these control strategies more feasible. This study evaluates potential long-term effects of the risk-based approach compared with non-risk-based strategies by simulations conducted with the herd-simulation model PTB-Simherd. Seven control strategies were simulated in herds with initial true herd prevalences of 5, 25, and 50%, respectively. The results predicted the risk-based control strategies to be very efficient and comparable to the best whole-herd strategies in reducing the within-herd prevalence of paratuberculosis with considerably less labor. If infection routes are closed efficiently, prevalence can be reduced to 10% of initial prevalence within 5 to 7 yr. Test-and-cull strategies without closing infection routes were found, by simulation, to be ineffective in reducing prevalence and were not cost-effective methods. The profitability of the various control strategies depends on hourly wages and time spent per cow/calving. Furthermore, simulations show that immediate culling of highly infectious cows is only necessary and cost-effective if infection routes from these cows are not efficiently closed. The risk-based control strategies are recommended in the Danish voluntary control program "Operation Paratuberculosis," which was initiated in February 2006 and now includes 1,220 dairy farmers in Denmark.