OBJECTIVES:  The Disease Burden Scale (DBS), a 4-item instrument derived from the Diabetes Burden Scale (Kaplan 2010), measures the impact of specific health conditions on a patient’s overall health, social activities, lifestyle and finances.  We sought to build on prior validation of the parent instrument by evaluating the validity and reproducibility of the DBS and testing equivalence between paper and electronic administration modes.  METHODS:  Adult patients with depression, type 2 diabetes, or rheumatoid arthritis were recruited through web-based advertisements in 8 U.S. cities and completed the DBS on both paper and computerized format in a randomized crossover design.  A one-week retest was also completed.  Reproducibility and mode equivalence were assessed using the intraclass correlation coefficient (ICC).  Cronbach’s alpha was calculated to assess internal consistency.  To assess convergent validity, the correlation of the DBS to the WHO Quality of Life Scale (WHOQOL-BREF) was calculated.  ANOVA was used to compare mean DBS scores among known groups defined by the MOS-36 MCS and PCS subscales. RESULTS:  Of the 230 participants that completed baseline assessment, 228 (99.1%) completed the one-week retest. The mean age of participants was 44.3 years, 51.3% were female, and 58.3% were Caucasian. A small amount (n=9; 3.9%) reported their health as Poor. The mean paper DBS score was 44.8 (±26.6), and the ICC between paper and computerized administration was 0.876. The ICC for the one-week retest of the paper format was 0.944, and the DBS was found to be internally consistent (Cronbach’s alpha=0.899). Significant correlations were found with the WHOQOL-BREF (r=0.460 to 0.646; p<0.01) and the instrument discriminated between hypothesized MOS-36 score groups (MCS, p<0.01; PCS, p<0.01). CONCLUSIONS:  The DBS was observed to be reproducible and internally consistent, demonstrated appropriate convergent validity, and significantly discriminated between levels of overall health status.  Equivalence between paper and web-based administration was demonstrated.