This paper describes an implementation of HMMER with FPGA. HMMER is one of the most used software tools for sensitive profile HMM (Hidden Markov Model) searches of biological sequence databases. HMMER is a very cpuintensive program. In HMMER, the Viterbi algorithm, which is a quadratic dynamic programming algorithm, is used to align a profile HMM and a protein sequence. In the profile HMM, a feedback path from the end of the model to the beginning is allowed, and this loop makes it difficult to process the Viterbi algorithm in parallel. In our approach, the alignment is calculated speculatively in parallel, and when the feedback path is selected in the alignment, the alignment is recalculated from the beginning using the fedback score. According to our experiments, the ratio that the feedback path is selected is very low, and the performance loss by the recalculation is less than a few percent. Another problem for accelerating HMMER using FPGA is the large size of the score tables required for profile HMMs. By crossing the search direction in the quadratic search space and the moving direction of each processing unit in the search space, we can minimize the size of the memory banks for storing the score tables. This optimization technique makes it possible to process all profile HMMs in a database efficiently.