OBJECTIVE: Many conditions have strong diurnal components which may influence work productivity. We evaluate the relationship between sleep impairment and productivity loss using symptomatic daytime vs. nighttime gastro-esophageal reflux disease (GERD) as an example. METHODS: An Internet survey of employed US adults measured GERD symptom frequency and severity (prior 12 months and prior seven days). GERD status was assessed with the validated GERD-SMQ. General health-related and GERD-specific productivity losses were evaluated using the WPAI questionnaire. Nighttime sleep impairment (SI) was assessed by a panel of six questions concerning sleep problems. Our conceptual framework modeled the impact of nighttime symptoms as causing SI which, in turn, influences daytime work productivity. Thus, two-equations: 1) SI as a function of GERD status (and covariates); and 2) WPAI as a function of SI (and covariates), were simultaneously estimated using three-stage least squares (3SLS) regression. Results were compared to those of an alternative instrumental variables specification. RESULTS: Of 65,001 individuals invited to participate, 13,231 (21.4%) responded. A total of 1002 were symptomatic GERD cases (476 nighttime vs. 526 daytime) which were included in the analysis. 3SLS showed nighttime vs. daytime GERD was associated with a significant increase in SI ? =33.6%, p<0.001). Respondents with severe or very severe GERD also experienced greater SI ? =39.1%, p<0.005). SI was shown to have a large impact on work productivity (elasticity = 5.4%, p<0.001). ?2 values were 384 (p<0.0001) and 84.5 (p<0.0001) for the first and second equations. 3SLS results were consistent with the IV specification. CONCLUSIONS: Nighttime GERD symptoms significantly impair sleep which results in reductions in daytime work productivity. The impact of the distinct diurnal nature of chronic conditions is little understood. This framework may prove useful in evaluating similar chronic health conditions (eg, asthma) and related adverse events due to medication use.