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Purpose: The purpose of this study was to assess the associations between demographic, professional and other personal nurse characteristics, social support factors and comfort in conducting research with nurses' level of active participation in clinical research. Design: A prospective, cross‐sectional, correlational design was used. Methods: Clinical nurses working in a multihospital healthcare system were recruited by email to complete an anonymous survey that used multiple valid and reliable scales to assess demographic and professional work characteristics, curiosity, grit, locus of control, perceived social support (for research activities), comfort in conducting research, and level of being research‐active. Univariate and multivariable analyses were completed. Results: Of 310 participants, 274 (88.4%) were female and mean (SD) age was 42.9 (13.1) years. After condensing 11 levels of research activity to four categories, 179 (57.7%) were not research‐active, and 91 (29.4%), 26 (8.3%) and 14 (4.5%) were engaged at low, moderate, and high levels, respectively. Of 78 factors, 69 (88.5%) were associated with being research‐active in univariate analyses. In multivariable analysis that adjusted for age, personal experience as a patient, years as a nurse and hours in direct patient care, professionalism characteristics, higher curiosity, internal locus of control, grit perseverance, support of a nurse scientist and nurse friends, and comfort in conducting research remained associated with higher levels of being research‐active (all p < 0.01). Conclusion: Research‐active nurses were more likely to be engaged professionally in hospital‐based activities beyond their work roles and displayed higher levels of positive psychological characteristics and mentorship that supported research capacity. Clinical Relevance: Research‐active nurses were more likely to have internal factors and external resources that promoted higher levels of being research‐active. A strong professional governance model may enhance clinical nurses research activities. [ABSTRACT FROM AUTHOR]