A one-year study to establish the container closure integrity (CCI) performance landscape of systems comprising rubber stoppers and glass vials was performed. Focus was on addressing the issues of CCI performance versus: (a) time, (b) compression levels and residual seal force (RSF) values, and (c) potential variation in results based upon the deterministic measurement method (tracer gas and frequency modulated spectroscopy). To reduce sample size to a manageable number, the study was based upon a design of experiments that considered a range of: (a) stopper formulations, sizes, and configurations; (b) vial sizes, types, and suppliers; and (c) compression levels. All systems showed good performance; there was no decrease in CCI with time, highlighting the general robustness of rubber-glass vial systems. Lower compression/RSF values tended to give slightly lower performance and wider scatter in data and thus should not be recommended for commercial applications. A small amount of oxygen exchange through the stoppers was observed for all systems-to be expected because rubber is known to be gas permeable. Consistent with models, RSF values decreased initially and then remained constant. Results are consistent with the literature.