Virus diseases represent important economic threats to the production of seed potatoes worldwide, yet little quantitative information is available on the relative merits of different measures of virus control applied singly or in combination. In this study, we compiled data from the national seed certification programme on the incidence of Potato Virus Y (PVY) and Potato Leaf-roll Virus (PLRV) in potato tubers in Switzerland for the years 1990–2009 and used generalised linear models to investigate the influence of key epidemiological factors on infection risk. Results showed that post-harvest virus incidence increased with initial inoculum levels, with the largest change in infection risk occurring between fields with no inoculum and those with low levels of inoculum. Virus incidence decreased with increasing altitude of fields. Surprisingly, infection risk was considerably lower for imported seed lots even though the model controlled for the effect of inoculum level, potato variety and other confounders. Overall, variety was the most important factor influencing virus risk. The results of the present analysis are useful to fine-tune decision-support systems that predict disease risk under different epidemiological scenarios.