Objectives: Concerns have been raised that isolation precautions may have unintended consequences. The relationship between patient isolation and the 30-day risk of readmission or death among patients discharged from a general medicine ward was examined. Methods: A prospective cohort study of adult patients discharged to the community from seven general internal medicine wards in Edmonton, Alberta, Canada, from October 2013 to November 2014, was performed. Patients under contact, respiratory, or droplet precautions were considered isolated. Covariates measured at discharge included the Charlson comorbidity score, LACE index, clinical frailty, depression, anxiety, health-related quality of life, and patient satisfaction. Outcomes were measured at 30 days by telephone follow-up and provincial electronic health record query. Results: Of 495 patients (mean age 62 years, 51% female), 75 (18%) were isolated during their admission. Isolated and non-isolated patients had similar lengths of stay (6.2 vs. 6.2 days), depression, anxiety, health-related quality of life, and satisfaction scores at discharge (all p-values non-significant). At 30 days, 85 (17.2%) patients had been readmitted or had died (20.0% of isolated patients vs. 16.7% of non-isolated patients; adjusted odds ratio 1.11, 95% confidence interval 0.57–2.18). Conclusions: In-hospital isolation does not appear to have an adverse impact on outcomes once patients are discharged from hospital.