Our purpose was to examine self‐efficacy of knee function, physical activity (PA) and health‐related quality of life (HRQoL) in post‐meniscectomy patients and controls as well as to explore the impact of gender and the association between outcomes. Ninety‐nine post‐meniscectomy patients (27% women), mean age 44.5 years, mean (range) of follow‐up time 3 (1–5) years, and 94 controls (34% women), mean age 45 years, completed the following questionnaires: the Knee Self‐Efficacy Scale (K‐SESABC), the Physical Activity Scale (PAS) and the Short Form‐36 (SF‐36). Patients scored lower than controls in K‐SESABC and in the SF‐36 subscales Physical Functioning and Bodily Pain (P≤0.002). Forty‐six percent of the patients had resumed pre‐injury PA, but current PA did not differ between the groups. In the patients, K‐SESABC correlated strongly with four physical SF‐36 subscales and one mental scale (Vitality) (rs=0.56–0.85, P<0.001) and moderately with three subscales: (rs=0.35–0.46, P<0.001) and with PAS (rs=0.42, P<0.001). Females scored lower than males in K‐SESABC (P=0.006) and in four SF‐36 subscales (P<0.04), but reported similar PA as men. We conclude that meniscectomy in middle‐aged individuals may lead to lower self‐efficacy of knee function, a sedentary lifestyle and poorer HRQoL.