Canadian patients, healthcare providers and payers share interest in assessing the value of self-monitoring of blood glucose (SMBG) for individuals with type 2 diabetes but not on insulin. Using the UKPDS (UK Prospective Diabetes Study) model, the Canadian Optimal Prescribing and Utilization Service (COMPUS) conducted an SMBG cost-effectiveness analysis. Based on the results, COMPUS does not recommend routine strip use for most adults with type 2 diabetes who are not on insulin. Cost-effectiveness studies require many assumptions regarding cohort, clinical effect, complication costs, etc. The COMPUS evaluation included several conservative assumptions that negatively impacted SMBG cost effectiveness. Current objectives were to (i) review key, impactful COMPUS assumptions; (ii) illustrate how alternative inputs can lead to more favourable results for SMBG cost effectiveness; and (iii) provide recommendations for assessing its long-term value. A summary of COMPUS methods and results was followed by a review of assumptions (for trial-based glycosylated haemoglobin [HbA(1c)] effect, patient characteristics, costs, simulation pathway) and their potential impact. The UKPDS model was used for a 40-year cost-effectiveness analysis of SMBG (1.29 strips per day) versus no SMBG in the Canadian payer setting. COMPUS assumptions for patient characteristics (e.g. HbA(1c) 8.4%), SMBG HbA(1c) advantage (-0.25%) and costs were retained. As with the COMPUS analysis, UKPDS HbA(1c) decay curves were incorporated into SMBG and no-SMBG pathways. An important difference was that SMBG HbA(1c) benefits in the current study could extend beyond the initial simulation period. Sensitivity analyses examined SMBG HbA(1c) advantage, adherence, complication history and cost inputs. Outcomes (discounted at 5%) included QALYs, complication rates, total costs (year 2008 values) and incremental cost-effectiveness ratios (ICERs). The base-case ICER was $Can63 664 per QALY gained; approximately 56% of the COMPUS base-case ICER. SMBG was associated with modest risk reductions (0.10-0.70%) for six of seven complications. Assuming an SMBG advantage of -0.30% decreased the current base-case ICER by over $Can10 000 per QALY gained. With adherence of 66% and 87%, ICERs were (respectively) $Can39 231 and $Can54 349 per QALY gained. Incorporating a more representative complication history and 15% complication cost increase resulted in an ICER of $Can49 743 per QALY gained. These results underscore the importance of modelling assumptions regarding the duration of HbA(1c) effect. The current study shares several COMPUS limitations relating to the UKPDS model being designed for newly diagnosed patients, and to randomized controlled trial monitoring rates. Neither study explicitly examined the impact of varying the duration of initial HbA(1c) effects, or of medication or other treatment changes. Because the COMPUS research will potentially influence clinical practice and reimbursement policy in Canada, understanding the impact of assumptions on cost-effectiveness results seems especially important. Demonstrating that COMPUS ICERs were greatly reduced through variations in a small number of inputs may encourage additional clinical research designed to measure SMBG effects within the context of optimal disease management. It may also encourage additional economic evaluations that incorporate lessons learned and best practices for assessing the overall value of SMBG for type 2 diabetes in insulin-naive patients.