Harm reduction strategies commonly include needle and syringe programmes (NSP), opioid substitution therapy (OST) and interventions combining these two strategies. Despite the proven effectiveness of harm-reduction strategies in reducing human immunodeficiency virus (HIV) infection among injecting drug users (IDUs), no study has compared the cost-effectiveness of these interventions, nor the incremental cost effectiveness of combined therapy. Using data from the Global Fund, this study compares the cost-effectiveness of harm reduction strategies in Eastern Europe and Central Asia, using the Ukraine as a case study.