Background: Spontaneous reporting of adverse drug reactions (ADRs) in hospitals is scarce and several obstacles to such reporting have been identified previously. Objective: To assess the effectiveness of a multifaceted intervention based on healthcare management agreements for improving spontaneous reporting of ADRs by physicians in a hospital setting. Methods: In 2003, the spontaneous reporting of ADRs was included as one of the objectives of hospital physicians at the Vall d'Hebron Hospital, Barcelona, Spain, within the context of management agreements between clinical services and hospital managers. A continuous intervention related to these management agreements, including periodic educational meetings and economic incentives, was then initiated. We carried out an ecological time series analysis and assessed the change in the total number of spontaneous reports of ADRs, and the number of serious ADRs, unexpected ADRs, and ADRs associated with new drugs between a period previous to the intervention (from 1998 to 2002) and the period during the intervention (from 2003 to 2005). A time series analysis with ARIMA (Auto-Regressive Integrated Moving Average) models was performed. Results: The median number of reported ADRs per year increased from 40 (range 23-55) in the first period to 224 (range 98-248) in the second period. In the first period, the monthly number of reported ADRs was stable (3.47 per month; 95% CI 1.90, 5.03), but in the second period the number increased progressively (increase of 0.74 per month; 95% CI 0.62, 0.86). In the second period, the proportion of reported serious ADRs increased nearly 2-fold (63.1% vs 32.5% in the first period). The absolute number of previously unknown or poorly known ADRs increased 4-fold in the second period (54 vs 13 in the first period). There was also an increase in the absolute number of suspected pharmacological exposures to new drugs (97 vs 28) and in the number of different new drugs suspected of causing ADRs (50 vs 19). Conclusion: A continuous intervention based on healthcare management agreements with economic incentives and educational activities is associated with a quantitative and qualitative improvement of spontaneous reporting of ADRs by hospital physicians. © 2009 Adis Data Information BV. All rights reserved.