BACKGROUND: Bacteraemia data are often used as a general measure of resistance prevalence but may poorly represent other infection types. We compared resistance prevalence between bloodstream infection (BSI) and lower respiratory tract infection (LRTI) isolates collected by the BSAC Resistance Surveillance Programme. METHODS: BSI isolates (n = 8912) were collected during 2014-18 inclusive and LRTI isolates (n = 6280) between October 2013 to September 2018 from participating laboratories in the UK and Ireland, to a fixed annual quota per species group. LRTI isolates, but not BSI, were selected by onset: community for Streptococcus pneumoniae; hospital for Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacterales. MICs were determined centrally by agar dilution; statistical modelling adjusted for ICU location and possible clustering by collection centre. RESULTS: Resistance was more prevalent among the LRTI isolates, even after adjusting for a larger proportion of ICU patients. LRTI P. aeruginosa and S. pneumoniae were more often resistant than BSI isolates for most antibiotics, and the proportion of MRSA was higher in LRTI. For S. pneumoniae, the observation reflected different serotype distributions in LRTI and BSI. Relationships between LRTI and resistance were less marked for Enterobacterales, but LRTI E. coli were more often resistant to β-lactams, particularly penicillin/β-lactamase inhibitor combinations, and LRTI K. pneumoniae to piperacillin/tazobactam. For E. cloacae there was a weak association between LRTI, production of AmpC enzymes and cephalosporin resistance. CONCLUSIONS: Estimates of resistance prevalence based upon bloodstream isolates underestimate the extent of the problem in respiratory isolates, particularly for P. aeruginosa, S. pneumoniae, S. aureus and, less so, for Enterobacterales.