Objective: To evaluate the indicators of activity and quality within the emergency department (ED) during a resident physicians' strike. Methods: This was an observational study comparing a strike period (SP) and a non-strike period (NSP) in the ED of a 1,000-bed tertiary care teaching hospital in Barcelona, Spain, with an annual census of 100,000 emergency visits. During a period of nine nonconsecutive days, the resident physicians were on strike. Emergency visits were handled by staff members. Data were compared between all patients treated in the ED during the SP and those treated during the NSP, matched by the weekday. The authors compared lengths of stay (LOSs), rates of use of laboratory tests and radiology procedures, numbers of patient walkouts, patient/physician ratios, emergency hospital admission rates, home discharge rates, unscheduled return rates, and mortality rates. Results: The two groups (SP 2,610 patients and NSP 3,634 patients) were comparable in terms of average daily attendance rate (SP: 290 ± 12 vs NSP: 302 ± 21; p = 0.13), elective hospital admission rate, and severity of illness. Statistically significant differences were found in terms of mean total patients' LOS (SP: 206.75 ± 12.27 vs NSP: 235.10 ± 27.08 minutes; p < 0.001), number of laboratory tests per patient (SP: 0.30 ± 0.05 vs NSP: 0.38 ± 0.04; p < 0.001), and radiographs per patient (SP: 0.78 ± 0.06 vs NSP: 0.88 ± 0.09; p = 0.021). Conclusions: This study demonstrated that replacing residents with staff physicians resulted in fewer laboratory tests ordered, fewer radiographs ordered, and shorter lengths of stays in the ED.