Objectives. Workplace violence (WV) is an important occupational hazard for healthcare workers (HCWs). Methods. A longitudinal study was carried out on HCWs from an infectious disease hospital. Work-related stress, anxiety, and depression were measured at baseline in 2003, and they were reassessed in 2005, along with the assaults that occurred in the previous year. Results. One-year prevalences of 6.2% and 13.9% were reported for physical and verbal aggressions, respectively. Perpetrators were mainly patients. The professional groups most frequently attacked were physicians, followed by nurses. Workers with job strain at baseline had a significant risk of being subject to aggression (OR 7.7; CI 95%, 3.3–17.9) in the following year. The relationship between job strain and subsequent WV remained significant even after correction for anxiety, depression, and other confounders. Conversely, experiencing WV was associated with a high risk of job strain and effort-reward imbalance in the following year. The final levels of anxiety and depression were predicted using regression models that included physical aggression among predictive variables. Conclusions. WV is the spark that sets off a problematic work situation. Effective prevention of WV can only be achieved within the framework of an overall improvement in the quality of work.