The efficacy and residue deposition patterns of different formulations of lincomycin hydrochloride and tylosin tartrate were examined for control of Paenibacillus larvae subsp. larvae, the causative agent of American foulbrood disease (AFB). In Canada and the U.S., oxytetracycline is the only currently registered antibiotic for control of bacterial brood diseases, however resistant strains of P. l. larvae are prevalent. Large-scale field trials were conducted in Northern Alberta to determine the efficacy lincomycin and tylosin formulated as sugar dustings and pollen patties against colonies with infections of oxytetracyline-resistant AFB. A target dose of 600 mg of antibiotic was administered to colonies either in single applications, or in one-third doses over successive weeks, during the spring or fall. In parallel experiments, the same formulations were applied and residue deposition profiles in honey were determined. To sample residues, 15 g of honey was drawn from brood nests and honey supers at weekly intervals, commencing one week after the last application of antibiotics to colonies; residues were determined by LC-ESI-MS/MS. Initial results suggest that lincomycin and tylosin can be formulated as sugar dustings or pollen patties with similar efficacy at controlling severe infections of AFB. Both drugs are extremely stable in honey and pose a potential residue risk when applied as sugar dustings during the in spring. When applied in fall, both formulations leave minimal residues in the harvested honey during the succeeding summer. Irrespective of application period, pollen patty formulations leave brood nest residues that are very low and are predominantly undetectable in harvested honey.