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The role of advanced practice providers has expanded in the hospital setting. However, little data exist examining the impact of these providers. Our purpose was to determine the effect of adding nurse practitioners in a complementary role on the quality and efficiency of care of hospitalized patients. A retrospective cohort study evaluated adult patients admitted by private physicians (without house staff or non-physician providers) to a general medical-surgical unit in an academic medical center. The admissions department allocated patients as beds became available and nurse practitioners were assigned to patients until their caseload was reached. Outcomes included length of hospital stay, in-hospital mortality, admission costs, 30-day readmissions, transfer to a more intensive care level, and discharge order time. Of the 382 patients included in this study, 263 were assigned to the nurse practitioner group. Hospital mortality was lower in the nurse practitioner group [OR 0.11 (95% CI 0.02–0.51)] as was transfer to more intensive care level [OR 0.39 (95% CI 0.20–0.75)]; however, the nurse practitioner group had longer length of stay (geometric mean = 5.80 days for nurse practitioners, 3.63 days for no nurse practitioners; p < 0.0001) and higher cost per patient (geometric mean = USD 6631 vs. USD 5121; p = 0.005). The results were unchanged when models were adjusted for potential confounders. Adding nurse practitioners can yield improved clinical outcomes (lower hospital mortality and fewer transfers to intensive care), but with a potential economic expense (longer hospital stays and higher costs).