BackgroundA haplotype is a set of DNA variants inherited together from one parent or chromosome. Haplotype information is useful for studying genetic variation and disease association. Haplotype assembly (HA) is a process of obtaining haplotypes using DNA sequencing data. Currently, there are many HA methods with their own strengths and weaknesses. This study focused on comparing six HA methods or algorithms: HapCUT2, MixSIH, PEATH, WhatsHap, SDhaP, and MAtCHap using two NA12878 datasets named hg19 and hg38. The 6 HA algorithms were run on chromosome 10 of these two datasets, each with 3 filtering levels based on sequencing depth (DP1, DP15, and DP30). Their outputs were then compared.ResultRun time (CPU time) was compared to assess the efficiency of 6 HA methods. HapCUT2 was the fastest HA for 6 datasets, with run time consistently under 2 min. In addition, WhatsHap was relatively fast, and its run time was 21 min or less for all 6 datasets. The other 4 HA algorithms’ run time varied across different datasets and coverage levels. To assess their accuracy, pairwise comparisons were conducted for each pair of the six packages by generating their disagreement rates for both haplotype blocks and Single Nucleotide Variants (SNVs). The authors also compared them using switch distance (error), i.e., the number of positions where two chromosomes of a certain phase must be switched to match with the known haplotype. HapCUT2, PEATH, MixSIH, and MAtCHap generated output files with similar numbers of blocks and SNVs, and they had relatively similar performance. WhatsHap generated a much larger number of SNVs in the hg19 DP1 output, which caused it to have high disagreement percentages with other methods. However, for the hg38 data, WhatsHap had similar performance as the other 4 algorithms, except SDhaP. The comparison analysis showed that SDhaP had a much larger disagreement rate when it was compared with the other algorithms in all 6 datasets.ConclusionThe comparative analysis is important because each algorithm is different. The findings of this study provide a deeper understanding of the performance of currently available HA algorithms and useful input for other users.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12863-023-01134-5.