Potato (Solanum tuberosum) is the third most important crop in the world after rice and wheat. Potato tubers are rich in starch, but also contain minor amounts of phenolic compounds. The chlorogenic acid isomer 5-O-caffeoylquinic acid (5-CQA) is the predominant phenolic acid in potato. The main aim of this study was to investigate the relationship between phenolic content and starch digestibility in vitro and in vivo. Firstly, the effect of 5-CQA on digestion of commercial potato starch by porcine pancreatic alpha amylase (PPAA) was investigated. The results showed that co- and pre-incubation of PPAA with 5-CQA significantly reduced PPAA activity in a dose dependent manner with an IC50 value of about 2 mg mL-1. Lineweaver-Burk plots indicated that 5-CQA exerts a mixed type inhibition as km increased and Vmax decreased. Secondly, in vitro starch digestion was performed on steam cooked tubers from five varieties of potato (Desiree, Mozart, Rooster, Maris Piper and Maris Peer) with varying phenolic content. 5-CQA content of peeled tuber tissue ranged from 10.36 to 29.46 mg 100g-1 dry weight (DW) in raw tubers and 6.51 to 21.24 mg 100g-1 DW in cooked tubers. With the exception of Desiree, 5-CQA levels decreased after cooking. The composition of the tubers in term of dry matter (DM), total starch (TS), free sugars, starch properties (amylose and starch granule structure) were also determined. Significant differences in digestibility by PPAA alone were observed between potato varieties when measured as area under curve (AUC) of glucose released in vitro (p ≤ 0.05). Rooster had the highest and Maris Piper the lowest AUC. Similar results were obtained when an in vitro digestion that simulated gastric (including pepsin) and intestinal (including amyloglucosidase AMG) digestion was used to calculate hydrolysis index (HI) and estimated glycaemic index (eGI). Finally, the digestibility of potato was measured in vivo using steamed tubers from Desiree, Rooster and Maris Piper. Standard glycaemic index (GI) methodology was followed. The results showed that Rooster has the highest GI (120), followed by Maris Piper (109) and Desiree (98). The differences were not statistically significant. Strong and positive correlations were observed between in vivo GI and eGI (p ≤ 0.01). It was observed that estimated glycaemic index (eGI) of cooked potato negatively correlated with 5-CQA (r=-0.91, p ≤ 0.05 ) and in vivo glycaemic response (GI) negatively correlated with TPC and 5-CQA (r =-0.82,-0.91) (p ≤ 0.05) respectively. Principle component analysis indicated that starch digestibility is affected by multiple factors including phenolic, dry matter, starch content, starch granule size and crystalline lamella structure. It appears that the same single factor does not strongly determine digestibility in all varieties.