The objectives of this one-year population-based cohort study was to describe and compare antibiotic and antipyretic/antiinflammatory drugs use, resolution of URTI symptoms and occurrence of potentially associated infections in patients who seek care for URTI from general practitioners showing different prescribing preferences for homeopathy: strictly prescribers of conventional medications reluctant to prescribe homeopathic medicines, regular prescribers of homeopathic medicines in an otherwise conventional medical practice, and certified homeopathic GPs, who also prescribe conventional medications. This population-based WZ8040 msds prospective cohort study described and compared clinical management and evolution of patients consulting for URTI between three groups of physicians with different levels of prescribing preferences for homeopathy. At baseline, patients who chose to be seen by GP-Ho for URTI declared to have used half the amount of antibiotics and antipyretic/antiinflammatory drugs compared to patients seen by conventional medicine practitioners. This lower consumption of conventional medications in the GP-Ho group was sustained over the 12-month follow-up. At the same time, no difference in the resolution of the URTI symptoms was observed between groups but confidence intervals were wide indicating lack of statistical power for that outcome. Similarly, the excess rate of potentially associated infections observed in the GP-Ho group, although non-statistically significant, cannot be ruled out. No difference was seen in patients from the GP-Mx group, which was comparable to the GP-CM group on all outcomes. Previous observational studies conducted in several countries have shown an antibiotic-sparing effect resulting from management by GPs using homeopathy without increase in complication rates of URTI. Patients’ education, including appropriate indication for antibiotic use, infection prognosis, and alternative treatment recommendations, may contribute to lower patients’ expectations toward antibiotics while improving satisfaction. This has been described in France during the 2009–2010 influenza season. Authors have pointed out the difficulty of sorting out patients’ expectations/motivation and homeopathic care itself, including their providers. The rise in bacterial resistance to antibiotics is widely recognized as a major threat to public health. Antibiotic prescribing for URTI varies widely within and across countries suggesting that further control of antibiotic prescribing is possible. Many countries have implemented policies aimed at reducing inappropriate prescribing of antimicrobials in primary care. In that context, our results are not unexpected and can contribute to reinforce the motivation of decision makers to pursue these policies. Our results could be explained in part by the different characteristics of patients seen by GPs who practice homeopathy and by the lower rate of fever, nasal obstruction and cough in the GP-Ho group at baseline compared to the two other groups. Adjustment by severity of URTI and other potential confounders did not alter the results but residual confounding cannot be excluded.