OBJECTIVES: To compare incremental cost effectiveness ratios (ICERs) obtained with different algorithms to relate quality of life (QoL) instruments to preference-based utilities. METHODS: We determined the ICER of treating primary insomnia with eszopiclone compared to placebo treatment based on a model developed using data from a 6-month, double-blind, placebo controlled, clinical trial to assess the quality-adjusted life years (QALYs) and costs associated with eszopiclone treatment. The average 6-month net cost per patient treated with eszopiclone versus placebo is $69 (2006 USD). QoL data were collected in the trial using the SF-36. Utilities were derived using 4 algorithms chosen for methodological merit (Brazier 2002), applicability to a US population (Franks 2003 & 2004, Lawrence 2004), and ability to generate an age- and gender-independent utility (all). All utilize either the SF-12 or the SF-6D subsets of the SF-36, but differ by: choice of utility mapped from the QoL instrument (standard gamble or EQ-5D); items or subscales of the instrument retained; weighting assigned to the items or subscales; source of the sample used to value the instrument (UK or US); and theoretical range of the predicted utility (e.g., Brazier ranges from 0.35 to 1.0 where Lawrence ranges from 0.15 to 1.01). Other algorithms were not analyzed because they were not generic measures, not preference-based, or excluded the vitality domain (a clinically relevant domain for patients with insomnia). RESULTS: The four algorithms resulted in average net gains in 6-month QALYs with eszopiclone over placebo of 0.006687, 0.012447, 0.013714, and 0.013800, for the Brazier, Lawrence, Franks (2004), and Franks (2003) algorithms, respectively. These data represent mean costs per QALY of $10,261, $5,513, $5,003, and $4,972, respectively. CONCLUSION: These algorithms, based on either SF-12 item responses or summary scales, generated cost effective yet different point estimates for net gain in utilities and the resulting ICERs.