The problem of antimicrobial resistance (AMR) is substantial, exacerbated by excessive and inappropriate antibiotic prescribing. Approximately 60% of antibiotics issued in primary care are for respiratory tract infections (RTIs), which are mostly self-limiting and do not require antibiotics. Point-of-care testing (POCT) devices that measure C-reactive protein (CRP) – a biomarker for infection – can be used to guide and ultimately reduce prescribing. We performed a cost-effectiveness and budget impact analysis of a national programme of CRP POCT to improve antimicrobial stewardship for RTIs in primary care in Ireland. We compared CRP POCT – with and without communication skills training of General Practitioners – against usual care. We performed a network meta-analysis to establish clinical effectiveness and developed a probabilistic decision tree to investigate cost-effectiveness and budget impact from the perspective of the healthcare system. The model considered outcomes for the Irish population over five years. Inputs were synthesised from published studies. Cost-effectiveness was estimated using cost-per-prescription avoided. CRP POCT with/out communication training was more costly and effective than usual care, although some uncertainty in long-term effectiveness was observed. CRP POCT without communication training was dominated, while the combined intervention had a cost-per-prescription avoided of €111 (95% CI €45 to €243) versus usual care. The budget impact was costly over five years, estimated at €4.5 million (95% CI €-22.8 to €34.8 million) and €23.9 million (95% CI €5.1 to €43.8 million) with/out communication training. The findings were robust to sensitivity analyses. CRP POCT is most cost-effective when combined with communication training. However, the budget impact is costly, and there’s limited evidence that the effect is sustained in the long-term, suggesting the device may not reflect value for money or sufficiently address the growing problem of AMR. CRP POCT should be considered alongside a suite of interventions aimed at improving antimicrobial stewardship.