Extant analyses of the relation between economic conditions and population health were often based on annualized data and were susceptible to confounding by nonlinear time trends. In the present study, the authors used generalized additive models with nonparametric smoothing splines to examine the association between economic conditions, including levels of economic activity in New York State and the degree of volatility in the New York Stock Exchange, and monthly rates of death by suicide in New York City. The rate of suicide declined linearly from 8.1 per 100,000 people in 1990 to 4.8 per 100,000 people in 1999 and then remained stable from 1999 to 2006. In a generalized additive model in which the authors accounted for long-term and seasonal time trends, there was a negative association between monthly levels of economic activity and rates of suicide; the predicted rate of suicide was 0.12 per 100,000 persons lower when economic activity was at its peak compared with when it was at its nadir. The relation between economic activity and suicide differed by race/ethnicity and sex. Stock market volatility was not associated with suicide rates. Further work is needed to elucidate pathways that link economic conditions and suicide.