Purpose: To simulate patient flow in proton treatment center under uncertainty and to explore the feasibility of treatment preparation rooms to improve patient throughput and cyclotron utilization. Methods: Three center layout scenarios were modeled: (S1: In-Tx room imaging) patient setup and imaging (planar/volumetric) performed in treatment room, (S2: Patient setup in preparation room) each treatment room was assigned with preparation room(s) that was equipped with lasers only for patient setup and gross patient alignment, and (S3: Patient setup and imaging in preparation room) preparation room(s) was equipped with laser and volumetric imaging for patient setup, gross and fine patient alignment. A 'snap' imaging was performed in treatment room. For each scenario, the number of treatment rooms and the number of preparation rooms serving each treatment room were varied. We examined our results (average of 100 16-hour (two shifts) working days) by evaluating patient throughput and cyclotron utilization. Results: When the number of treatment rooms increased ([from, to]) [1, 5], daily patient throughput increased [32, 161], [29, 184] and [27, 184] and cyclotron utilization increased [13%, 85%], [12%, 98%], and [11%, 98%] for scenarios S1, S2 and S3 respectively. However, both measures plateaued after 4 rooms. With the preparation rooms, themore » throughput and the cyclotron utilization increased by 14% and 15%, respectively. Three preparation rooms were optimal to serve 1-3 treatment rooms and two preparation rooms were optimal to serve 4 or 5 treatment rooms. Conclusion: Patient preparation rooms for patient setup may increase throughput and decrease the need for additional treatment rooms (cost effective). Optimal number of preparation rooms serving each gantry room varies as a function of treatment rooms and patient setup scenarios. A 5th treatment room may not be justified by throughput or utilization.« less