Introduction Workers can reduce their risk of exposure to hazardous drugs by following safe handling guidelines. Healthcare centers need to dedicate time and resources in order to implement new safety recommendations. The objective was to present the results of a national survey about the safe handling of hazardous drugs in healthcare centers. Methods Quebec healthcare centers performed an auto-evaluation to the newly updated safe handling guidelines in 2021. Centers rated each criterion as compliant or non-compliant. The guidelines tailored recommendations according to three categories of hazards: G1, consisting mostly of carcinogenic drugs; G2, other hazardous drugs; and G3, those with reproductive toxicity. The questionnaire prompted participants to document their planned corrective measures for non-compliant criteria. Results Most centers participated (28/29, 97%). The overall compliance was 58% (8761/15,216 criteria). The conformity per theme was hygiene and sanitation (1290/1,878, 69%), laundry (221/367, 60%), pharmacy (2658/4,474, 59%), nursing (3436/6,017, 57%), spills and accidental exposure (353/649, 54%), and general measures (803/1,831, 44%). It was higher for recommendations regarding G1s (4226/6,115, 69%) than for G2s (1626/3557, 46%) and G3s (372/916, 41%). Conclusions This project successfully used an innovative approach that combined a national auto-evaluation survey, an actionable report, and the involvement of a community of practice. Centers were able to benchmark their implementation of safe handling guidelines, and community of practices may help in sharing the best practices. The design of the questionnaire helped in targeting corrective measures. More work is needed for safe handling practices that relate to G2 and G3 drugs.