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This paper presents the design, analysis, and implementation of parallel and sequential I/O-efficient algorithms for set cover, tying together the line of work on parallel set cover and the line of work on efficient set cover algorithms for large, disk-resident instances. Our contributions are twofold: First, we design and analyze a parallel cache-oblivious set-cover algorithm that offers essentially the same approximation guarantees as the standard greedy algorithm, which has the optimal approximation. Our algorithm is the first efficient external-memory or cache-oblivious algorithm for when neither the sets nor the elements fit in memory, leading to I/O cost (cache complexity) equivalent to sorting in the Cache Oblivious or Parallel Cache Oblivious models. The algorithm also implies elow cache misses on parallel hierarchical memories (again, equivalent to sorting). Second, building on this theory, we engineer variants of the theoretical algorithm optimized for different hardware setups. We provide experimental evaluation showing substantial speedups over existing algorithms without compromising the solution's quality.