People who inject drugs (PWID) are a key high-risk group for Hepatitis C Virus (HCV) infection due to the sharing of needles and drug-preparation equipment. However, only approximately 50% of PWID are currently screened for HCV in Switzerland. At present, screening of PWID occurs in general practice via venepuncture. Compared to venepuncture, screening via rapid antibody saliva and dried blood spot (DBS) tests is well adapted to PWID, who typically have difficult venous access. The cost-effectiveness of an increased access screening programme of PWID (increased screening using rapid antibody saliva tests and DBS tests [semi-quantitative viraemia and viral genotype]) was analysed through a decision tree screening model combined with the outputs of a Markov treatment model. Sensitivity and scenario analyses examined the uncertainty of results. At a willingness to pay (WTP) threshold of CHF 100 000 (USD 105 000) per quality-adjusted life year (QALY), the increased access screening programme was cost-effective compared to current screening, with a base case incremental cost-effectiveness ratio of CHF 7 940 (USD 8337) per QALY. The net monetary benefit was CHF 959 802 668 (USD 1 007 792 801) for the PWID population and CHF 94 469 (USD 99 192) per person. The increased access screening programme had a 97.0% probability of being cost-effective compared to the current screening method at the WTP threshold of CHF 100 000 (USD 105 000). The results showed an increased access screening programme that uses tests which are better suited to the PWID population to be more cost-effective, due to the increased uptake that rapid antibody saliva and DBS tests generate.