Objective: The authors investigated the association between death of older people and use of psychotropic drugs before and during the Western European August 2003 heatwave., Method: A retrospective population-based case-control study was conducted using the French social security insurance national database. Exposure to psychotropic drugs in cases aged 70-100 years who died before (N = 2,093) and during (N = 9,531) the August 2003 heatwave was compared with those of survivors matched for age, gender, and presence of chronic illness, by using conditional logistic regressions., Results: The association between death and psychotropic drug use was modified by level of external temperature (Wald chi(2) = 13.1, degree of freedom = 1, p <0.001). Use of any psychotropic drug was associated with a 30% increased risk of death during the heatwave, with a significant dose-response relationship between the number of psychotropic drugs and the risk of death (adjusted odds ratio [aOR] for linear trend 1.25, 95% confidence interval [95% CI]: 1.21-1.29). During the heatwave, therapeutic classes independently associated with an increased risk of death were antidepressants (aOR 1.71, 95% CI: 1.57-1.86) and antipsychotics (aOR 2.09, 95% CI: 1.89-2.35), whereas exposure to anxiolytics/hypnotics use (aOR 0.85, 0.79-0.91) was associated with a decreased risk. Findings remained unchanged after adjustment on cardiotropic, antidementia, or anti-parkinsonian drug use., Conclusion: Our findings suggest that a causal relationship may exist between psychotropic drug use during a heatwave and increased risk of death in older people. The risk/benefit ratio of antidepressant and antipsychotic drugs should be carefully assessed in older people during a heatwave.