The 1918 influenza pandemic known as the "Spanish Flu" has been the worst in recent history with estimated worldwide mortality ranging from 20 to 100 million deaths. Using epidemic modeling and hospital notification data during the 1918 influenza pandemic in the Canton of Geneva, Switzerland, we estimated the reproductive numbers of the first and second waves of influenza infection to be R(1)=1.49 (95% CI: 1.45-1.53) and R(2)=3.75 (95% CI: 3.57-3.93), respectively. Our estimates indicate that containment of the next influenza pandemic could require strict interventions that include effective isolation strategies in hospitals and reductions in the susceptibility of the general population.