The purpose of this study was to explore the relationship between hospital-level indicators of the work environment and aggregated indicators of health and well-being amongst registered nurses working in acute-care hospitals in Ontario, Canada. This ecological analysis used data from a self-reported survey instrument randomly allocated to nurses using a stratified sampling approach. Multivariable linear regression models were used to examine hospital-level associations for burnout, musculoskeletal pain, self-rated general health, and absence due to illness. The unit of analysis was the hospital (n = 160), with individual nurse responses (n = 6,609) aggregated within hospitals. After controlling for basic differences in nurse workforces, including mean age and education, higher (better) work-environment scores were found to be generally associated with higher health-indicator scores, while a larger proportion of full-time than part-time nurses was found to be associated with lower (poorer) health scores. This study may provide direction for policy-makers in coping with the recruitment and retention of nursing staff in light of the current nursing shortage.