Objective: To examine the epidemiological association between sudden deterioration leading to death and Tamiflu use. Design: Proportional mortality study. Setting: Japan. Participants: 162 deaths without deterioration before the first consultation among all 198 deaths of mostly confirmed 2009A/H1N1 influenza. Population at risk: Age-specific population of influenza patients prescribed Tamiflu and Relenza. Main outcome measure: Age-stratified pooled odds ratio (OR) for early (within 12 hours) deterioration and overall death of Tamiflu prescribed to Relenza prescribed patients. Results: Of 119 deaths after Tamiflu was prescribed, 38 deteriorated within 12 hours (28 within 6 hours), while of 15 deaths after Relenza, none deteriorated within 12 hours. Pooled OR for early deterioration and overall death were 5.88 (95% CI: 1.30 to 26.6, p = 0.014) and 1.91 (p = 0.031) respectively. Baseline characteristics including risk factors did not contribute to early deterioration after Tamiflu use. Conclusions: These data suggest Tamiflu use could induce sudden deterioration leading to death especially within 12 hours of prescription. These findings are consistent with sudden deaths observed in a series of animal toxicity studies, several reported case series and the results of prospective cohort studies. From “the precautionary principle” the potential harm of Tamiflu should be taken into account and further detailed studies should be conducted.