The effect of Direct Healthcare Professional Communications (DHPCs) informing health-care providers of serious drug safety issues has been questioned. The aim of this study was to evaluate the impact of DHPCs on drug use. Nationwide dispensing data for the period 2000-2008 for new users of 46 drugs with one or more DHPCs were assessed. Impact on short-term volume of use was evaluated with regression models, and the presence of long-term changes in use was evaluated with interrupted time series analyses incorporating preexisting trends. The short-term prescription level was lower post-DHPC in 28 (48.3%) of 58 cases. Twenty (34.5%) DHPCs resulted in long-term changes in use. A long-term mean reduction in use was observed in 26.7% of cases (95% confidence interval, -15.2 to -38.2%). Long-term changes in use were not significantly related to preexisting trends in use. Although short- and long-term decreases in use were observed after only half and a third of DHPCs, respectively, the decrease was substantial.