The advent of affordable, shared-nothing computing systems portends a new class of parallel database management systems (DBMS) for on-line transaction processing (OLTP) applications that scale without sacrificing ACID guarantees [7, 9]. The performance of these DBMSs is predicated on the existence of an optimal database design that is tailored for the unique characteristics of OLTP workloads [43]. Deriving such designs for modern DBMSs is difficult, especially for enterprise-class OLTP systems, since they impose extra challenges: the use of stored procedures, the need for load balancing in the presence of time-varying skew, complex schemas, and deployments with larger number of partitions. To this purpose, we present a novel approach to automatically partitioning databases for enterprise-class OLTP systems that significantly extends the state of the art by: (1) minimizing the number distributed transactions, while concurrently mitigating the effects of temporal skew in both the data distribution and accesses, (2) extending the design space to include replicated secondary indexes, (4) organically handling stored procedure routing, and (3) scaling of schema complexity, data size, and number of partitions. This effort builds on two key technical contributions: an analytical cost model that can be used to quickly estimate the relative coordination cost and skew for a given workload and a candidate database design, and an informed exploration of the huge solution space based on large neighborhood search. To evaluate our methods, we integrated our database design tool with a high-performance parallel, main memory DBMS and compared our methods against both popular heuristics and a state-of-the-art research prototype [17]. Using a diverse set of benchmarks, we show that our approach improves throughput by up to a factor of 16 × over these other approaches.