BackgroundNeedle and syringe programs (NSP) are effective harm-reduction strategies against HIV and hepatitis C. Although skin, soft tissue, and vascular infections (SSTVI) are the most common morbidities in people who inject drugs (PWID), the extent to which NSP are clinically and cost-effective in relation to SSTVI in PWID remains unclear. The objective of this study was to model the clinical- and cost-effectiveness of NSP with respect to treatment of SSTVI in PWID.MethodsWe performed a model-based, economic evaluation comparing a scenario with NSP to a scenario without NSP. We developed a microsimulation model to generate two cohorts of 100,000 individuals corresponding to each NSP scenario and estimated quality-adjusted life-years (QALY) and cost (in 2022 Canadian dollars) over a 5-year time horizon (1.5% per annum for costs and outcomes). To assess the clinical effectiveness of NSP, we conducted survival analysis that accounted for the recurrent use of health care services for treating SSTVI and SSTVI mortality in the presence of competing risks.ResultsThe incremental cost-effectiveness ratio associated with NSP was $70,278 per QALY, with incremental cost and QALY gains corresponding to $1207 and 0.017 QALY, respectively. Under the scenario with NSP, there were 788 fewer SSTVI deaths per 100,000 PWID, corresponding to 24% lower relative hazard of mortality from SSTVI (hazard ratio [HR] = 0.76; 95% confidence interval [CI] = 0.72–0.80). Health service utilization over the 5-year period remained lower under the scenario with NSP (outpatient: 66,511 vs. 86,879; emergency department: 9920 vs. 12,922; inpatient: 4282 vs. 5596). Relatedly, having NSP was associated with a modest reduction in the relative hazard of recurrent outpatient visits (HR = 0.96; 95% CI = 0.95–0.97) for purulent SSTVI as well as outpatient (HR = 0.88; 95% CI = 0.87–0.88) and emergency department visits (HR = 0.98; 95% CI = 0.97–0.99) for non-purulent SSTVI.ConclusionsBoth the individuals and the healthcare system benefit from NSP through lower risk of SSTVI mortality and prevention of recurrent outpatient and emergency department visits to treat SSTVI. The microsimulation framework provides insights into clinical and economic implications of NSP, which can serve as valuable evidence that can aid decision-making in expansion of NSP services.