In multiple-effect distillers with horizontal tubes, which are increasingly employed in seawater desalination, scale formation on the heat transfer surfaces has a highly deleterious effect on specific energy consumption and production capacity. The allowance for potential scale formation by over-sizing the heat transfer surface, scale prevention methods, cleaning methods as well as production losses during plant shutdown for cleaning create considerable capital, operating, and maintenance costs. It is therefore essential to incorporate a cost-effective scale control technique. In multiple-effect distillers scale is formed on the outside of the tubes. Mechanical cleaning methods can-not be employed. Achieving effective scale control by suitable anti-scalants is a major challenge for the desalination industry. Scale formation and control in multiple-effect distillers with horizontal tubes for seawater desalination have barely been investigated. The effects of the process parameters and of the anti-scalants on the properties of the scale, e.g., the composition, structure, and morphology, are inadequately understood. Clarifying these aspects of scale formation would facilitate further improvement of anti-scalants and thus the efficiency of multiple-effect distillers. In order to study scale formation and control under conditions that are close to those prevailing in industrial multiple-effect distillers, a horizontal tube evaporator at pilot-plant scale was employed. In the test rig the process conditions in any stage and at various operating conditions of multiple-effect distillers can be provided. Thus, the effects of the thermal field, the flow field, the fluid properties, and the substrate properties can be studied. Experiments with artificial seawater were performed at different operating conditions. Novel aspects of the formation and reduction of scales formed from falling seawater films on the outside of horizontal tubes are presented. The effects of various process conditions such as fluid temperature, heat transfer surface temperature, heat flux, and seawater salinity on the composition and structure of scale layers are shown. The beneficial effects of polymeric anti-scalants on the quantity, composition, and morphology of the scale are discussed. For example, the use of only 0.5 ppm of a specific anti-scalant effectuated a very strong reduction of the calcium carbonate content in the scale as well as a notable decline of the magnesium hydroxide content.