The Revised Strain Index (RSI), a model that quantifies physical exposure from individual hand/ wrist exertions, tasks, and multi-task jobs, was used to quantify exposure for 1372 incident-eligible manufacturing, service and healthcare workers. Workers were followed for an average of 2.5 years (maximum 6 years) and had an average carpal tunnel syndrome (CTS) incidence rate of 4.6 per 100 person-years. Exceeding the a-priori RSI limit of 10.0 showed increased risk of CTS (Hazard Ratio (HR) ¼ 1.45, 95% CI: 1.11-1.91, p ¼ 0.01). There also was a dose-response relationship using proposed low (RSI 8.5, HR ¼ 1.00), medium (HR ¼ 1.42 (95% CI: 0.96-2.09, p ¼ 0.08)), and high limits (RSI > 15, HR ¼ 1.79 (95% CI: 1.19-2.69, p ¼ 0.01), respectively. RSI as a continuous variable showed CTS risk increased steadily by between 1.9% and 3.3% per unit increase in RSI (p 0.03). These results suggest that the RSI is a useful tool for surveillance as well as for job intervention/design and continuous improvement processes. Practitioner Summary The Revised Strain Index (RSI) quantifies physical exposure from individual hand/wrist exertions, tasks, and multi-task jobs. Increased cumulative RSI scores (i.e. daily exposure score) are associated with increased risk of carpal tunnel syndrome (CTS). The RSI is potentially useful as a risk surveillance and intervention design tool.