Failure of metal roof is the most commonly observed damage in cyclones. Significant numbers of metal roof coverings, corners, and eaves are damaged. International codes of practice specify the procedure for the calculation of structural capacity of purlins supporting standing-seam metal roof (SSMR) systems, but they do not specify the procedure to design the panel-purlin connection system, integrated by a clip called a halter. The panel profiles and fastening techniques adopted worldwide are so diverse that the strength of panel-purlin connection and the lateral restraint on purlin by diaphragm action cannot be generalized. However, the type of standing-seam system presented in this paper, viz., the clip lock system, is prevalent in many countries with uniformity in halter dimensions and seam heights. The details of an experimental investigation on prototype cold-formed steel (CFS) standing-seam clip lock system tested under wind uplift in a vacuum chamber are presented here. A vacuum chamber was fabricated specially for this purpose, as per standards. The behavior and failure modes of rigid purlin-panel system were studied. Experimental data on the uplift behavior of SSMR were gathered. This data were converted to design parameters through statistical evaluation. Three limit states of panel-purlin interaction failure were studied and a procedure for the integral design of SSMR halter-rigid purlin systems was developed, guided by the experimental results. On the design effect side, four wind-pressure cases, along with cyclonic wind pressure, were considered. The applicability of the experimental results to practical designs was quantified by a reliability-based analysis. Based on the values of reliability indices, the zones of failure were identified, and a rational design of variable halter length was proposed. The halter length could be adjusted as per the target reliability, leading to the concept of SSMR roof system with a uniform safety. © 2018 American Society of Civil Engineers.