Limited knowledge exists about the factors that may influence nurse practitioner (NP) patient panel size. Patient panel size refers to the number of patients for whom a NP is their usual care provider. Increased knowledge of these factors may improve patient care, NP practice, and primary health care (PHC) workforce planning. Two hundred and eighty-three NPs working in Ontario PHC were surveyed to explore patient, NP, and organizational factors that may influence NP patient panel size. Three factors were associated with NP panel size. Higher percentages of certain health conditions and/or longer appointment time for multi-morbid and palliative care were associated with smaller NP patient panel size. NPs who worked more hours per week had larger patient panels. Also, the PHC practice model was related to NP patient panel size, which was largest in NP-led clinics. Decision makers can use these findings to support optimization of NP patient panel size.