Details of the development of early knee osteoarthritis (OA) are largely unknown. The prevalence and progression of radiographic knee OA over 6 years in middle-aged subjects with chronic knee pain is investigated. In a prospective population-based study, tibiofemoral (TF) and patellofemoral (PF) radiographs were graded in 128 subjects (mean age 45 ± 6.2 years) for the presence of osteophytes and joint space narrowing (JSN). Radiographic progression was defined as: (i) the presence of osteophytes and/or JSN in subjects with no previous OA or (ii) an increase in the grade and/or number of already existing osteophytes and/or JSN. Altogether 56% (72/128) of subjects had knee OA, the majority of them was diagnosed with OA grade 1. In 57% of cases, radiographic OA was based on the presence of osteophytes alone versus 13% on JSN. More than 1/3 of subjects had isolated PF joint involvement. Knee OA progression rate over 6 years was 56% (71/128). During 6 years, a non-linear course of radiographic OA progression with intermittent periods of progression and stabilization was observed. Individual course of OA revealed distinct subsets of radiographic progression. Osteophytosis is an important early radiographic sign of OA and its progression. Isolated PF joint involvement is a frequent expression of knee OA. In middle-aged subjects, the progression rate of knee OA over 6 years was 56%. A non-linear course of radiographic OA progression was observed. Several radiographic subsets refer to the heterogeneity of the OA process.